Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Sarcoma That Cannot Be Removed by Surgery

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02500797
• Collaborator: (none)
• Enrollment: 164
• Locations: 651
• Arms: 2
• Anticipated Duration (Months): 84.4
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well nivolumab with or without ipilimumab works in treating patients with sarcoma that has spread from the primary site to other parts of the body (metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether nivolumab works better with or without ipilimumab in treating patients with metastatic or unresectable sarcoma.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Bone Sarcoma; Locally Advanced Dedifferentiated Liposarcoma; Locally Advanced Gastrointestinal Stromal Tumor; Locally Advanced Soft Tissue Sarcoma; Metastatic Bone Sarcoma; Metastatic Liposarcoma; Metastatic Soft Tissue Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Metastatic Unresectable Sarcoma; Pleomorphic Liposarcoma; Stage III Bone Sarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Bone Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Stage IVA Bone Sarcoma AJCC v7; Stage IVB Bone Sarcoma AJCC v7; Unresectable Bone Sarcoma; Unresectable Dedifferentiated Liposarcoma; Unresectable Liposarcoma; Unresectable Malignant Gastrointestinal Stromal Tumor; Unresectable Soft Tissue Sarcoma	Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Quality-of-Life Assessment	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. To evaluate the confirmed response rate of single agent nivolumab and dual agent nivolumab plus ipilimumab in patients with locally advanced/unresectable or metastatic soft tissue sarcoma.

SECONDARY OBJECTIVES:

1. To evaluate adverse event rates (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]4.0) within each treatment arm.

2. To evaluate duration of response, clinical benefit rate, time to progression, progression-free survival, and overall survival within each treatment arm.

CORRELATIVE SCIENCE OBJECTIVES:

1. To potentially detect an early signal of confirmed response rate within a histologically defined patient cohort.

2. To assess the potential association between programmed cell death 1 ligand 1 (PD-L1) expression (by immunohistochemistry [IHC]) and clinical outcome, within each treatment.

3. To evaluate associations between selected biomarker measured in serial peripheral blood and with clinical efficacy, within each treatment.

4. To evaluate the association between selected biomarker measured in tumor tissue with clinical efficacy, within each treatment.

5. To evaluate the association between baseline tumor mutational burden and neoantigen production with clinical efficacy within each treatment.

EXPLORATORY PHASE II OBJECTIVES (CROSSOVER TREATMENT):

1. To evaluate secondary endpoints within patients crossing over to dual agent nivolumab plus ipilimumab after experiencing progressive disease while receiving single agent nivolumab.

2. To evaluate correlative science objectives endpoints within patients crossing over to dual agent nivolumab plus ipilimumab after experiencing progressive disease while receiving single agent nivolumab.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress after 10 weeks on single agent nivolumab may elect to cross over to Arm II.

ARM II: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.

After completion of study treatment, patients are followed up at 4 weeks and then every 6 months 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 164 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Study of Nivolumab With or Without Ipilimumab in Patients With Metastatic or Unresectable Sarcoma
• Actual Study Start Date: Jul 30, 2015
• Actual Primary Completion Date: Apr 1, 2019
• Anticipated Study Completion Date: Aug 10, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (nivolumab) Patients receive nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress after 10 weeks on single agent nivolumab may elect to cross over to Arm II.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Nivolumab; Given IV; Other Names: BMS-936558 CMAB819 MDX-1106 NIVO Nivolumab Biosimilar CMAB819 ONO-4538 Opdivo ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment
Experimental: Arm II (nivolumab, ipilimumab) Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Biological: Ipilimumab; Given IV; Other Names: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody BMS-734016 Ipilimumab Biosimilar CS1002 MDX-010 MDX-CTLA4 Yervoy ; Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Nivolumab; Given IV; Other Names: BMS-936558 CMAB819 MDX-1106 NIVO Nivolumab Biosimilar CMAB819 ONO-4538 Opdivo ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Achieved a Confirmed Response [Up to 44 months]

   The number of participants who achieved a confirmed response is defined as the number of patients having a best objective tumor status of complete response (CR) or partial response (PR) lasting at least 4 weeks as determined using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites).

Secondary Outcome Measures

1. Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event Regardless of Attribution [Up to 4 weeks after completion of study treatment]

   The number of participants who experienced at least one grade 3 or higher adverse event (AE) regardless of attribution. AEs are graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 beginning April 1, 2018).

2. Duration of Response [Time from first response to progression, assessed up to 3 years]

   Duration of response is defined for all evaluable patients who have achieved a confirmed response as the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression (PD) is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by >= 50% of previously involved sites from nadir).

3. 6-Month Clinical Benefit Rate [Initial Cohort] [At 6 months]

   The 6-month clinical benefit rate is defined as the percentage of participants with a response or stable disease (CR, PR, or SD) at 6 months. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by >= 50% of previously involved sites from nadir, SD: Not CR/PR or PD).

4. 6-Month Clinical Benefit Rate [Expansion LPS and UPS/MFH Cohorts Only] [At 6 months]

   The 6-month clinical benefit rate is defined as the percentage of participants with a response or stable disease (CR, PR, or SD) at 6 months. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by >= 50% of previously involved sites from nadir, SD: Not CR/PR or PD).

5. 6-Month Clinical Benefit Rate [Expansion GIST Cohort Only] [At 6 months]

   The 6-month clinical benefit rate is defined as the percentage of participants with a response or stable disease (CR, PR, or SD) at 6 months. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by >= 50% of previously involved sites from nadir, SD: Not CR/PR or PD).

6. Progression-free Survival (PFS) [Time from randomization to first of either disease progression or death from any cause, assessed up to 3 years]

   Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression (PD) is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. (PD: Any new lesion or increase by >= 50% of previously involved sites from nadir).

7. Overall Survival (OS) [Time from randomization to death from any cause, assessed up to 3 years]

   Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

Other Outcome Measures

1. PD-L1 Expression Assessed Using Immunohistochemistry (IHC) [Up to 3 years]

   Categorical data analysis and logistic regression will be used to evaluate the associations between PD-L1 expression (by IHC) and clinical outcome (e.g., response, clinical benefit, progression-free survival, and survival). Kaplan-Meier methodology and Cox proportional hazards models will be used to evaluate time to event endpoints.

2. Change in Selected Biomarkers Measured in Serial Peripheral Blood [Baseline to up to 3 years]

   Summary statistics will be used to for describing changes across time. The time course of biomarker outcomes will be investigated graphically, by summary plots or individual patient plots. If there is suggestion of meaningful trend, methods such as linear mixed models may be used to characterize the pattern of change over time. Kaplan-Meier methodology and Cox proportional hazards models will be used to evaluate time to event endpoints.

3. Selected Biomarkers Measured in Tumor Tissue [Up to week 6]

   Categorical data analysis and logistic regression will be used to correlated biomarkers with and clinical outcome (e.g., response, clinical benefit, time to progression, progression free survival, and survival) within each study component. Kaplan-Meier methodology and Cox proportional hazards models will be used to evaluate time to event endpoints.

4. Confirmed Response in Patients Who Crossover From Single Agent Nivolumab to Dual Agent Treatment Following Progression [Up to 3 years]

   Confirmed response will be evaluated in patients who crossover from single agent nivolumab to dual agent treatment following progression.

5. Duration of Response in Patients Who Crossover From Single Agent Nivolumab to Dual Agent Treatment Following Progression [Time from first response to progression, assessed up to 3 years]

   Evaluated using Kaplan-Meier methodology.

6. PFS in Patients Who Crossover From Single Agent Nivolumab to Dual Agent Treatment Following Progression [Time from randomization to first of either disease progression or death from any cause, assessed up to 3 years]

   Evaluated using Kaplan-Meier methodology.

7. OS in Patients Who Crossover From Single Agent Nivolumab to Dual Agent Treatment Following Progression [Time from randomization to death from any cause, assessed up to 3 years]

   Evaluated using Kaplan-Meier methodology.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• PRE-REGISTRATION ELIGIBILITY CRITERIA:

• Patients must have a formalin-fixed, paraffin-embedded (FFPE) tumor block OR 1 representative hematoxylin and eosin (H&E) and 20 unstained sarcoma tissue slides available for submission to central pathology review; this review is mandatory prior to registration to confirm eligibility

• REGISTRATION ELIGIBILITY CRITERIA:

• Patients must have histologically confirmed bone or soft tissue sarcoma by central pathology review

• Patients must have histologically confirmed liposarcoma (LPS) (only dedifferentiated and pleomorphic; well differentiated not eligible), undifferentiated pleomorphic sarcoma (UPS)/malignant fibrous histiocytoma (MFH), or gastrointestinal stromal tumor (GIST)

• Measurable disease

• Locally advanced/unresectable or metastatic disease

• = 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy

• No prior therapy with ipilimumab or nivolumab, or any agent targeting programmed cell death 1 (PD-1), PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)

• No treatment with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation =< 28 days before study registration; no treatment with nitrosourea or mitomycin =< 42 days before study registration; for GIST, tyrosine kinase inhibitor can be continued for up to 3 days prior to initiation of study treatment

• Patients should have resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, version 4.0, grade 1 or less

• No history of the following:

• Active known or suspected autoimmune disease

• Patients with human immunodeficiency virus (HIV) are eligible if the lymphocytes

350 cluster of differentiation (CD)4+ cells and no detectable viral load

• Symptomatic, untreated, or uncontrolled brain metastases present

• Active autoimmune colitis

• Autoimmune panhypopituitarism

• Autoimmune adrenal insufficiency

• Known active hepatitis B or C

• Hepatitis B can be defined as:

• Hepatitis B surface antigen (HBsAg) > 6 months

• Serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) 20,000 IU/ml (105 copies/ml), lower values 2,000-20,000 IU/ml (104-105 copies/ml) are often seen in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B

• Persistent or intermittent elevation in alanine aminotransferase (ALT)/alanine aminotransferase (AST) levels

• Liver biopsy showing chronic hepatitis with moderate or severe necroinflammation

• Hepatitis C can be defined as:

• Hepatitis C antibody (Ab) positive

• Presence of hepatitis C virus (HCV) ribonucleic acid (RNA)

• Known active pulmonary disease with hypoxia defined as:

• Oxygen saturation < 85% on room air or

• Oxygen saturation < 88% despite supplemental oxygen

• No systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of registration

• Not pregnant and not nursing because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects; therefore for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Absolute neutrophil count (ANC) >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance > 45 mL/min using the lean body mass formula only (Modified Cockcroft and Gault; Shargel and Yu 1985)

• Total bilirubin =< 1.5 x upper limit of normal (ULN) in absence of Gilbert disease (total bilirubin =< 3 x ULN with Gilbert); also, if hyperbilirubinemia is clearly attributed to liver metastases total bilirubin =< 3 x ULN is permitted

• AST/ALT =< 3 x upper limit of normal (ULN)

• Thyroid stimulating hormone (TSH) within normal limits (WNL); supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH if free T4 is normal and patient is clinically euthyroid, patient is eligible

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Measurable disease

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Locally advanced/unresectable or metastatic disease

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Patient MUST have had progressive disease (radiographic or clinical) while on arm 1 single agent nivolumab while registered to A091401

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Patients removed from any immunotherapy for reasons other than progressive disease, including arm 1 single agent nivolumab of A091401, are NOT eligible for re-registration

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Patients must have completed a minimum of 10 weeks of single agent nivolumab on arm 1 of A091401 to be eligible for re-registration

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Patients must have completed study drug on arm 1 of A091401 (i.e., last dose of nivolumab) =< 12 months of re-registration to crossover dual agent therapy

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): No treatment with immunotherapy =< 21 days before re-registration; no treatment with biologic therapy, chemotherapy, investigational agent for malignancy, or radiation =< 28 days before re-registration; no treatment with nitrosourea or mitomycin =< 42 days before re-registration

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Patients should have resolution of any toxic effects of prior therapy (except fatigue and alopecia) to NCI CTCAE, version 4.0, grade 1 or less, including immune toxicity

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): No systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of re-registration

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Not pregnant and not nursing because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects; therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to re-registration is required

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): ECOG performance status 0 or 1

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): ANC >= 1,500/mm^3

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Platelet count >= 100,000/mm^3

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Creatinine =< 1.5 ULN OR calc. creatinine clearance > 45 mL/min (using lean body mass formula only [Modified Cockcroft and Gault; Shargel and Yu 1985])

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): Total bilirubin =< 1.5 x ULN in absence of Gilbert disease (total bilirubin =< 3 x ULN with Gilbert); if hyperbilirubinemia is clearly attributed to liver metastases, total bilirubin =< 3 x ULN is permitted

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): AST/ALT =< 3 x ULN

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR PATIENTS WHO CROSSOVER FROM ARM 1 NIVOLUMAB ALONE TO DUAL AGENT NIVOLUMAB AND IPILIMUMAB UPON PROGRESSION): TSH WNL; supplementation is acceptable to achieve a TSH WNL; in patients with abnormal TSH, if free T4 is normal and patient is clinically euthyroid, patient is eligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anchorage Associates in Radiation Medicine	Anchorage	Alaska	United States	98508
2	Anchorage Radiation Therapy Center	Anchorage	Alaska	United States	99504
3	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
4	Alaska Oncology and Hematology LLC	Anchorage	Alaska	United States	99508
5	Alaska Regional Hospital	Anchorage	Alaska	United States	99508
6	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
7	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
8	Katmai Oncology Group	Anchorage	Alaska	United States	99508
9	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
10	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas	United States	71913
11	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
12	Kaiser Permanente-Anaheim	Anaheim	California	United States	92806
13	Kaiser Permanente-Deer Valley Medical Center	Antioch	California	United States	94531
14	PCR Oncology	Arroyo Grande	California	United States	93420
15	Sutter Auburn Faith Hospital	Auburn	California	United States	95602
16	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California	United States	95603
17	Kaiser Permanente-Baldwin Park	Baldwin Park	California	United States	91706
18	Kaiser Permanente-Bellflower	Bellflower	California	United States	90706
19	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
20	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
21	Mills-Peninsula Medical Center	Burlingame	California	United States	94010
22	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California	United States	95682
23	Eden Hospital Medical Center	Castro Valley	California	United States	94546
24	Community Cancer Institute	Clovis	California	United States	93611
25	University Oncology Associates	Clovis	California	United States	93611
26	Sutter Davis Hospital	Davis	California	United States	95616
27	Kaiser Permanente-Fontana	Fontana	California	United States	92335
28	Kaiser Permanente-Fremont	Fremont	California	United States	94538
29	Palo Alto Medical Foundation-Fremont	Fremont	California	United States	94538
30	Kaiser Permanente-Fresno	Fresno	California	United States	93720
31	Kaiser Permanente - Harbor City	Harbor City	California	United States	90710
32	Kaiser Permanente-Irvine	Irvine	California	United States	92618
33	Loma Linda University Medical Center	Loma Linda	California	United States	92354
34	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
35	Kaiser Permanente West Los Angeles	Los Angeles	California	United States	90034
36	Memorial Medical Center	Modesto	California	United States	95355
37	Kaiser Permanente-Modesto	Modesto	California	United States	95356
38	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
39	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California	United States	94040
40	Sutter Cancer Research Consortium	Novato	California	United States	94945
41	Kaiser Permanente-Oakland	Oakland	California	United States	94611
42	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
43	Kaiser Permanente - Panorama City	Panorama City	California	United States	91402
44	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
45	Kaiser Permanente-Richmond	Richmond	California	United States	94801
46	Kaiser Permanente-Riverside	Riverside	California	United States	92505
47	Kaiser Permanente-Roseville	Roseville	California	United States	95661
48	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California	United States	95661
49	Sutter Roseville Medical Center	Roseville	California	United States	95661
50	Kaiser Permanente Downtown Commons	Sacramento	California	United States	95814
51	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
52	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
53	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
54	Kaiser Permanente-San Diego Mission	San Diego	California	United States	92108
55	Kaiser Permanente-San Diego Zion	San Diego	California	United States	92120
56	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
57	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
58	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
59	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
60	Kaiser Permanente-San Marcos	San Marcos	California	United States	92078
61	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
62	Kaiser San Rafael-Gallinas	San Rafael	California	United States	94903
63	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
64	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California	United States	95065
65	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
66	Sutter Pacific Medical Foundation	Santa Rosa	California	United States	95403
67	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
68	Kaiser Permanente-Stockton	Stockton	California	United States	95210
69	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California	United States	94086
70	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California	United States	95687
71	Kaiser Permanente Medical Center-Vacaville	Vacaville	California	United States	95688
72	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
73	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
74	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
75	Kaiser Permanente-Woodland Hills	Woodland Hills	California	United States	91367
76	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado	United States	80012
77	The Medical Center of Aurora	Aurora	Colorado	United States	80012
78	University of Colorado Hospital	Aurora	Colorado	United States	80045
79	Boulder Community Hospital	Boulder	Colorado	United States	80301
80	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado	United States	80304
81	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
82	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado	United States	80907
83	UCHealth Memorial Hospital Central	Colorado Springs	Colorado	United States	80909
84	Denver Health Medical Center	Denver	Colorado	United States	80204
85	Kaiser Permanente-Franklin	Denver	Colorado	United States	80205
86	The Women's Imaging Center	Denver	Colorado	United States	80209
87	Porter Adventist Hospital	Denver	Colorado	United States	80210
88	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
89	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
90	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado	United States	80218
91	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
92	Rocky Mountain Cancer Centers-Rose	Denver	Colorado	United States	80220
93	Rose Medical Center	Denver	Colorado	United States	80220
94	Mercy Medical Center	Durango	Colorado	United States	81301
95	Southwest Oncology PC	Durango	Colorado	United States	81301
96	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado	United States	80113
97	Swedish Medical Center	Englewood	Colorado	United States	80113
98	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
99	Mountain Blue Cancer Care Center	Golden	Colorado	United States	80401
100	National Jewish Health-Western Hematology Oncology	Golden	Colorado	United States	80401
101	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81501
102	North Colorado Medical Center	Greeley	Colorado	United States	80631
103	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado	United States	80111
104	Good Samaritan Medical Center	Lafayette	Colorado	United States	80026
105	Kaiser Permanente-Rock Creek	Lafayette	Colorado	United States	80026
106	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado	United States	80228
107	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
108	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado	United States	80120
109	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
110	Kaiser Permanente-Lone Tree	Lone Tree	Colorado	United States	80124
111	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado	United States	80124
112	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
113	Longmont United Hospital	Longmont	Colorado	United States	80501
114	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado	United States	80501
115	McKee Medical Center	Loveland	Colorado	United States	80539
116	Parker Adventist Hospital	Parker	Colorado	United States	80138
117	Rocky Mountain Cancer Centers-Parker	Parker	Colorado	United States	80138
118	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
119	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado	United States	81008
120	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado	United States	80260
121	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
122	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
123	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut	United States	06510
124	Yale University	New Haven	Connecticut	United States	06520
125	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
126	Beebe Medical Center	Lewes	Delaware	United States	19958
127	Christiana Gynecologic Oncology LLC	Newark	Delaware	United States	19713
128	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
129	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
130	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
131	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
132	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
133	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware	United States	19973
134	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
135	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
136	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
137	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
138	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida	United States	33180
139	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
140	Baptist MD Anderson Cancer Center	Jacksonville	Florida	United States	32207
141	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
142	Low Country Cancer Care	Savannah	Georgia	United States	31404
143	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
144	Summit Cancer Care-Memorial	Savannah	Georgia	United States	31404
145	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
146	Summit Cancer Care-Candler	Savannah	Georgia	United States	31405
147	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
148	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii	United States	96701
149	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii	United States	96701
150	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii	United States	96813
151	Island Urology	Honolulu	Hawaii	United States	96813
152	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii	United States	96813
153	Queen's Medical Center	Honolulu	Hawaii	United States	96813
154	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
155	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
156	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii	United States	96817
157	Kuakini Medical Center	Honolulu	Hawaii	United States	96817
158	Queen's Cancer Center - Kuakini	Honolulu	Hawaii	United States	96817
159	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii	United States	96817
160	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii	United States	96819
161	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
162	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
163	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
164	Saint Luke's Cancer Institute - Boise	Boise	Idaho	United States	83712
165	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho	United States	83605
166	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho	United States	83814
167	Walter Knox Memorial Hospital	Emmett	Idaho	United States	83617
168	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho	United States	83619
169	Idaho Urologic Institute-Meridian	Meridian	Idaho	United States	83642
170	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho	United States	83642
171	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho	United States	83686
172	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho	United States	83686
173	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho	United States	83854
174	Kootenai Cancer Clinic	Sandpoint	Idaho	United States	83864
175	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho	United States	83301
176	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
177	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
178	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
179	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
180	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
181	SIH Cancer Institute	Carterville	Illinois	United States	62918
182	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
183	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
184	Rush University Medical Center	Chicago	Illinois	United States	60612
185	Carle on Vermilion	Danville	Illinois	United States	61832
186	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
187	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
188	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
189	Crossroads Cancer Center	Effingham	Illinois	United States	62401
190	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
191	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
192	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
193	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
194	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois	United States	60026
195	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois	United States	60035
196	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
197	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
198	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
199	Loyola University Medical Center	Maywood	Illinois	United States	60153
200	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
201	Edward Hospital/Cancer Center	Naperville	Illinois	United States	60540
202	Cancer Care Center of O'Fallon	O'Fallon	Illinois	United States	62269
203	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
204	Radiation Oncology of Northern Illinois	Ottawa	Illinois	United States	61350
205	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
206	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
207	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
208	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois	United States	61615
209	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
210	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
211	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
212	Valley Radiation Oncology	Peru	Illinois	United States	61354
213	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois	United States	60585
214	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
215	North Shore Medical Center	Skokie	Illinois	United States	60076
216	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
217	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
218	Springfield Clinic	Springfield	Illinois	United States	62702
219	Memorial Medical Center	Springfield	Illinois	United States	62781
220	Southwest Illinois Health Services LLP	Swansea	Illinois	United States	62226
221	Carle Cancer Center	Urbana	Illinois	United States	61801
222	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
223	Rush-Copley Healthcare Center	Yorkville	Illinois	United States	60560
224	Deaconess Clinic Downtown	Evansville	Indiana	United States	47713
225	Parkview Hospital Randallia	Fort Wayne	Indiana	United States	46805
226	Parkview Regional Medical Center	Fort Wayne	Indiana	United States	46845
227	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
228	Woodland Cancer Care Center	Michigan City	Indiana	United States	46360
229	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana	United States	46545
230	Chancellor Center for Oncology	Newburgh	Indiana	United States	47630
231	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
232	Mary Greeley Medical Center	Ames	Iowa	United States	50010
233	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
234	McFarland Clinic PC-Boone	Boone	Iowa	United States	50036
235	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
236	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
237	Alegent Health Mercy Hospital	Council Bluffs	Iowa	United States	51503
238	Greater Regional Medical Center	Creston	Iowa	United States	50801
239	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
240	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
241	Broadlawns Medical Center	Des Moines	Iowa	United States	50314
242	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
243	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
244	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
245	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa	United States	50501
246	Trinity Regional Medical Center	Fort Dodge	Iowa	United States	50501
247	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
248	McFarland Clinic PC-Jefferson	Jefferson	Iowa	United States	50129
249	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa	United States	50158
250	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
251	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
252	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
253	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
254	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
255	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
256	Central Care Cancer Center - Garden City	Garden City	Kansas	United States	67846
257	Central Care Cancer Center - Great Bend	Great Bend	Kansas	United States	67530
258	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
259	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
260	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
261	Kansas Institute of Medicine Cancer and Blood Center	Lenexa	Kansas	United States	66219
262	Minimally Invasive Surgery Hospital	Lenexa	Kansas	United States	66219
263	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
264	Cancer Center of Kansas-Manhattan	Manhattan	Kansas	United States	66502
265	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
266	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
267	Menorah Medical Center	Overland Park	Kansas	United States	66209
268	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
269	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
270	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
271	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
272	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
273	Associates In Womens Health	Wichita	Kansas	United States	67208
274	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
275	Ascension Via Christi Hospitals Wichita	Wichita	Kansas	United States	67214
276	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
277	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
278	Flaget Memorial Hospital	Bardstown	Kentucky	United States	40004
279	Commonwealth Cancer Center-Corbin	Corbin	Kentucky	United States	40701
280	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky	United States	40504
281	Saint Joseph Hospital East	Lexington	Kentucky	United States	40509
282	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
283	Saint Joseph London	London	Kentucky	United States	40741
284	Jewish Hospital	Louisville	Kentucky	United States	40202
285	Saints Mary and Elizabeth Hospital	Louisville	Kentucky	United States	40215
286	UofL Health Medical Center Northeast	Louisville	Kentucky	United States	40245
287	Jewish Hospital Medical Center South	Shepherdsville	Kentucky	United States	40165
288	Ochsner Health Center-Summa	Baton Rouge	Louisiana	United States	70809
289	Medical Center of Baton Rouge	Baton Rouge	Louisiana	United States	70816
290	Ochsner Medical Center Kenner	Kenner	Louisiana	United States	70065
291	Ochsner LSU Health Monroe Medical Center	Monroe	Louisiana	United States	71202
292	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
293	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana	United States	71103
294	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
295	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland	United States	21237
296	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
297	Northwest Hospital Center	Randallstown	Maryland	United States	21133
298	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
299	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
300	Mercy Medical Center	Springfield	Massachusetts	United States	01104
301	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
302	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
303	Saint Joseph Mercy Brighton	Brighton	Michigan	United States	48114
304	Trinity Health IHA Medical Group Hematology Oncology - Brighton	Brighton	Michigan	United States	48114
305	Saint Joseph Mercy Canton	Canton	Michigan	United States	48188
306	Trinity Health IHA Medical Group Hematology Oncology - Canton	Canton	Michigan	United States	48188
307	Caro Cancer Center	Caro	Michigan	United States	48723
308	Saint Joseph Mercy Chelsea	Chelsea	Michigan	United States	48118
309	Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital	Chelsea	Michigan	United States	48118
310	Hematology Oncology Consultants-Clarkston	Clarkston	Michigan	United States	48346
311	Newland Medical Associates-Clarkston	Clarkston	Michigan	United States	48346
312	Beaumont Hospital - Dearborn	Dearborn	Michigan	United States	48124
313	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
314	Great Lakes Cancer Management Specialists-Doctors Park	East China Township	Michigan	United States	48054
315	Beaumont Hospital - Farmington Hills	Farmington Hills	Michigan	United States	48336
316	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan	United States	48503
317	Genesee Hematology Oncology PC	Flint	Michigan	United States	48503
318	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
319	Hurley Medical Center	Flint	Michigan	United States	48503
320	Academic Hematology Oncology Specialists	Grosse Pointe Woods	Michigan	United States	48236
321	Great Lakes Cancer Management Specialists-Van Elslander Cancer Center	Grosse Pointe Woods	Michigan	United States	48236
322	Michigan Breast Specialists-Grosse Pointe Woods	Grosse Pointe Woods	Michigan	United States	48236
323	William Beaumont Hospital-Grosse Pointe	Grosse Pointe	Michigan	United States	48230
324	Allegiance Health	Jackson	Michigan	United States	49201
325	Sparrow Hospital	Lansing	Michigan	United States	48912
326	Hope Cancer Clinic	Livonia	Michigan	United States	48154
327	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan	United States	48154
328	Great Lakes Cancer Management Specialists-Macomb Medical Campus	Macomb	Michigan	United States	48044
329	Michigan Breast Specialists-Macomb Township	Macomb	Michigan	United States	48044
330	Saint Mary's Oncology/Hematology Associates of Marlette	Marlette	Michigan	United States	48453
331	21st Century Oncology-Pontiac	Pontiac	Michigan	United States	48341
332	Hope Cancer Center	Pontiac	Michigan	United States	48341
333	Newland Medical Associates-Pontiac	Pontiac	Michigan	United States	48341
334	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
335	Huron Medical Center PC	Port Huron	Michigan	United States	48060
336	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
337	Great Lakes Cancer Management Specialists-Rochester Hills	Rochester Hills	Michigan	United States	48309
338	Michigan Cancer Specialists	Roseville	Michigan	United States	48066
339	Oakland Colon Rectal Associates	Royal Oak	Michigan	United States	48067
340	Cancer Care Associates PC	Royal Oak	Michigan	United States	48073
341	Comprehensive Medical Center PLLC	Royal Oak	Michigan	United States	48073
342	Hematology Oncology Consultants PC	Royal Oak	Michigan	United States	48073
343	Oakland Medical Group	Royal Oak	Michigan	United States	48073
344	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
345	Ascension Saint Mary's Hospital	Saginaw	Michigan	United States	48601
346	Oncology Hematology Associates of Saginaw Valley PC	Saginaw	Michigan	United States	48604
347	Bhadresh Nayak MD PC-Sterling Heights	Sterling Heights	Michigan	United States	48312
348	Premier Hematology Oncology Care	Sterling Heights	Michigan	United States	48312
349	Mitchell Folbe MD PC	Sterling Heights	Michigan	United States	48314
350	Ascension Saint Joseph Hospital	Tawas City	Michigan	United States	48764
351	Michigan Institute of Urology-Town Center	Troy	Michigan	United States	48084
352	Claudia BR Herke MD PC	Troy	Michigan	United States	48085
353	William Beaumont Hospital - Troy	Troy	Michigan	United States	48085
354	Hematology Oncology Consultants PC-Troy	Troy	Michigan	United States	48098
355	Advanced Breast Care Center PLLC	Warren	Michigan	United States	48088
356	Great Lakes Cancer Management Specialists-Macomb Professional Building	Warren	Michigan	United States	48093
357	Macomb Hematology Oncology PC	Warren	Michigan	United States	48093
358	Michigan Breast Specialists-Warren	Warren	Michigan	United States	48093
359	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
360	Saint Mary's Oncology/Hematology Associates of West Branch	West Branch	Michigan	United States	48661
361	Huron Gastroenterology PC	Ypsilanti	Michigan	United States	48106
362	Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus	Ypsilanti	Michigan	United States	48197
363	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota	United States	56601
364	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota	United States	56401
365	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
366	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
367	Essentia Health - Deer River Clinic	Deer River	Minnesota	United States	56636
368	Essentia Health Saint Mary's - Detroit Lakes Clinic	Detroit Lakes	Minnesota	United States	56501
369	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
370	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
371	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
372	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
373	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota	United States	56537
374	Essentia Health - Fosston	Fosston	Minnesota	United States	56542
375	Unity Hospital	Fridley	Minnesota	United States	55432
376	Essentia Health Hibbing Clinic	Hibbing	Minnesota	United States	55746
377	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota	United States	55369
378	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
379	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
380	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
381	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
382	Health Partners Inc	Minneapolis	Minnesota	United States	55454
383	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
384	Essentia Health - Park Rapids	Park Rapids	Minnesota	United States	56470
385	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
386	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
387	Regions Hospital	Saint Paul	Minnesota	United States	55101
388	United Hospital	Saint Paul	Minnesota	United States	55102
389	Essentia Health Sandstone	Sandstone	Minnesota	United States	55072
390	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
391	Lakeview Hospital	Stillwater	Minnesota	United States	55082
392	Sanford Thief River Falls Medical Center	Thief River Falls	Minnesota	United States	56701
393	Essentia Health Virginia Clinic	Virginia	Minnesota	United States	55792
394	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
395	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
396	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
397	Sanford Cancer Center Worthington	Worthington	Minnesota	United States	56187
398	Fairview Lakes Medical Center	Wyoming	Minnesota	United States	55092
399	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
400	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
401	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri	United States	63628
402	Cox Cancer Center Branson	Branson	Missouri	United States	65616
403	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
404	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
405	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
406	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
407	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
408	Freeman Health System	Joplin	Missouri	United States	64804
409	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
410	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
411	Research Medical Center	Kansas City	Missouri	United States	64132
412	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
413	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
414	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
415	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
416	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
417	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
418	Siteman Cancer Center-South County	Saint Louis	Missouri	United States	63129
419	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
420	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
421	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
422	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
423	CoxHealth South Hospital	Springfield	Missouri	United States	65807
424	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
425	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
426	Billings Clinic Cancer Center	Billings	Montana	United States	59101
427	Saint Vincent Healthcare	Billings	Montana	United States	59101
428	Saint Vincent Frontier Cancer Center	Billings	Montana	United States	59102
429	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
430	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
431	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
432	Saint Peter's Community Hospital	Helena	Montana	United States	59601
433	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
434	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
435	Community Medical Hospital	Missoula	Montana	United States	59804
436	CHI Health Saint Francis	Grand Island	Nebraska	United States	68803
437	Heartland Hematology and Oncology	Kearney	Nebraska	United States	68845
438	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
439	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska	United States	68510
440	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
441	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
442	Hematology and Oncology Consultants PC	Omaha	Nebraska	United States	68122
443	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
444	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
445	Creighton University Medical Center	Omaha	Nebraska	United States	68131
446	Midlands Community Hospital	Papillion	Nebraska	United States	68046
447	Carson Tahoe Regional Medical Center	Carson City	Nevada	United States	89703
448	Cancer and Blood Specialists-Henderson	Henderson	Nevada	United States	89052
449	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada	United States	89052
450	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada	United States	89052
451	Las Vegas Cancer Center-Henderson	Henderson	Nevada	United States	89052
452	OptumCare Cancer Care at Seven Hills	Henderson	Nevada	United States	89052
453	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada	United States	89074
454	GenesisCare USA - Henderson	Henderson	Nevada	United States	89074
455	Desert West Surgery	Las Vegas	Nevada	United States	89102
456	OptumCare Cancer Care at Charleston	Las Vegas	Nevada	United States	89102
457	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
458	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada	United States	89106
459	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada	United States	89106
460	GenesisCare USA - Las Vegas	Las Vegas	Nevada	United States	89109
461	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada	United States	89109
462	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada	United States	89113
463	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada	United States	89119
464	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada	United States	89121
465	Ann M Wierman MD LTD	Las Vegas	Nevada	United States	89128
466	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada	United States	89128
467	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada	United States	89128
468	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada	United States	89128
469	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada	United States	89128
470	OptumCare Cancer Care at MountainView	Las Vegas	Nevada	United States	89128
471	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada	United States	89144
472	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
473	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada	United States	89148-2405
474	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89148
475	GenesisCare USA - Fort Apache	Las Vegas	Nevada	United States	89148
476	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada	United States	89148
477	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada	United States	89149
478	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada	United States	89169
479	University Cancer Center	Las Vegas	Nevada	United States	89169
480	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada	United States	89048
481	Renown Regional Medical Center	Reno	Nevada	United States	89502
482	Saint Mary's Regional Medical Center	Reno	Nevada	United States	89503
483	Radiation Oncology Associates	Reno	Nevada	United States	89509
484	Ocean Medical Center	Brick	New Jersey	United States	08724
485	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
486	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
487	Bayshore Community Hospital	Holmdel	New Jersey	United States	07733
488	Southern Ocean County Medical Center	Manahawkin	New Jersey	United States	08050
489	Cooper CyberKnife Center	Mount Laurel	New Jersey	United States	08054
490	Jersey Shore Medical Center	Neptune	New Jersey	United States	07753
491	Riverview Medical Center/Booker Cancer Center	Red Bank	New Jersey	United States	07701
492	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey	United States	08043
493	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
494	New Mexico Oncology Hematology Consultants	Albuquerque	New Mexico	United States	87109
495	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico	United States	88011
496	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
497	Glens Falls Hospital	Glens Falls	New York	United States	12801
498	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
499	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
500	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
501	AdventHealth Infusion Center Asheville	Asheville	North Carolina	United States	28803
502	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
503	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina	United States	28328
504	AdventHealth Infusion Center Haywood	Clyde	North Carolina	United States	28721
505	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina	United States	27534
506	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
507	Hendersonville Hematology and Oncology at Pardee	Hendersonville	North Carolina	United States	28791
508	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
509	AdventHealth Hendersonville	Hendersonville	North Carolina	United States	28792
510	Onslow Memorial Hospital	Jacksonville	North Carolina	United States	28546
511	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina	United States	28546
512	Vidant Oncology-Kinston	Kinston	North Carolina	United States	28501
513	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
514	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota	United States	58103
515	Sanford South University Medical Center	Fargo	North Dakota	United States	58103
516	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
517	Sanford Clinic North-Fargo	Fargo	North Dakota	United States	58122
518	Sanford Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
519	Essentia Health - Jamestown Clinic	Jamestown	North Dakota	United States	58401
520	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
521	Bethesda North Hospital	Cincinnati	Ohio	United States	45242
522	TriHealth Cancer Institute-Westside	Cincinnati	Ohio	United States	45247
523	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio	United States	45255
524	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
525	Hematology Oncology Center Incorporated	Elyria	Ohio	United States	44035
526	Mercy Cancer Center-Elyria	Elyria	Ohio	United States	44035
527	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
528	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma	United States	73120
529	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
530	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon	United States	97814
531	Saint Charles Health System	Bend	Oregon	United States	97701
532	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
533	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon	United States	97015
534	Bay Area Hospital	Coos Bay	Oregon	United States	97420
535	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
536	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon	United States	97914
537	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
538	Providence Portland Medical Center	Portland	Oregon	United States	97213
539	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
540	Kaiser Permanente Northwest	Portland	Oregon	United States	97227
541	Saint Charles Health System-Redmond	Redmond	Oregon	United States	97756
542	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
543	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
544	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania	United States	19317
545	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
546	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
547	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania	United States	17837
548	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
549	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
550	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania	United States	17901
551	Community Medical Center	Scranton	Pennsylvania	United States	18510
552	Geisinger Medical Oncology-Selinsgrove	Selinsgrove	Pennsylvania	United States	17870
553	Geisinger Medical Group	State College	Pennsylvania	United States	16801
554	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
555	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina	United States	29316
556	Medical University of South Carolina	Charleston	South Carolina	United States	29425
557	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
558	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina	United States	29341
559	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina	United States	29601
560	Saint Francis Hospital	Greenville	South Carolina	United States	29601
561	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
562	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
563	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
564	Saint Francis Cancer Center	Greenville	South Carolina	United States	29607
565	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
566	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
567	Gibbs Cancer Center-Pelham	Greer	South Carolina	United States	29651
568	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
569	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
570	MGC Hematology Oncology-Union	Union	South Carolina	United States	29379
571	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota	United States	57104
572	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
573	Memorial Hospital	Chattanooga	Tennessee	United States	37404
574	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee	United States	37343
575	Memorial GYN Plus	Ooltewah	Tennessee	United States	37363
576	Saint Joseph Regional Cancer Center	Bryan	Texas	United States	77802
577	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
578	University of Vermont Medical Center	Burlington	Vermont	United States	05401
579	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
580	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington	United States	98520
581	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
582	Swedish Cancer Institute-Eastside Oncology Hematology	Bellevue	Washington	United States	98005
583	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
584	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
585	Harrison Medical Center	Bremerton	Washington	United States	98310
586	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
587	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
588	Swedish Cancer Institute-Edmonds	Edmonds	Washington	United States	98026
589	Saint Elizabeth Hospital	Enumclaw	Washington	United States	98022
590	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
591	Saint Francis Hospital	Federal Way	Washington	United States	98003
592	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
593	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
594	Providence Regional Cancer System-Lacey	Lacey	Washington	United States	98503
595	Saint Clare Hospital	Lakewood	Washington	United States	98499
596	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
597	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
598	Minor and James Medical PLLC	Seattle	Washington	United States	98104
599	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
600	Swedish Medical Center-Ballard Campus	Seattle	Washington	United States	98107
601	Kaiser Permanente Washington	Seattle	Washington	United States	98112
602	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
603	Swedish Medical Center-Cherry Hill	Seattle	Washington	United States	98122-5711
604	PeaceHealth United General Medical Center	Sedro-Woolley	Washington	United States	98284
605	Providence Regional Cancer System-Shelton	Shelton	Washington	United States	98584
606	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington	United States	99216
607	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington	United States	99204
608	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
609	MultiCare Deaconess Cancer and Blood Specialty Center - North	Spokane	Washington	United States	99218
610	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington	United States	98405
611	Northwest Medical Specialties PLLC	Tacoma	Washington	United States	98405
612	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
613	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
614	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
615	Providence Regional Cancer System-Yelm	Yelm	Washington	United States	98597
616	Edwards Comprehensive Cancer Center	Huntington	West Virginia	United States	25701
617	Duluth Clinic Ashland	Ashland	Wisconsin	United States	54806
618	Northwest Wisconsin Cancer Center	Ashland	Wisconsin	United States	54806
619	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
620	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
621	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin	United States	54937
622	Aurora Health Care Germantown Health Center	Germantown	Wisconsin	United States	53022
623	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
624	Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
625	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin	United States	53142
626	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin	United States	54143
627	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
628	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin	United States	53209
629	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
630	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
631	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53233
632	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
633	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
634	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
635	Aurora Cancer Care-Racine	Racine	Wisconsin	United States	53406
636	Lakeview Medical Center-Marshfield Clinic	Rice Lake	Wisconsin	United States	54868
637	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin	United States	54868
638	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
639	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
640	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin	United States	54482
641	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066
642	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin	United States	54241
643	Marshfield Clinic-Wausau Center	Wausau	Wisconsin	United States	54401
644	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin	United States	53226
645	Aurora West Allis Medical Center	West Allis	Wisconsin	United States	53227
646	Marshfield Medical Center - Weston	Weston	Wisconsin	United States	54476
647	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
648	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming	United States	82001
649	Big Horn Basin Cancer Center	Cody	Wyoming	United States	82414
650	Billings Clinic-Cody	Cody	Wyoming	United States	82414
651	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Sandra P D'Angelo, Alliance for Clinical Trials in Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 22, 2019

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02500797
• Other Study ID Numbers: NCI-2015-00260; NCI-2015-00260; A091401; A091401; A091401; U10CA180821
• First Posted: Jul 17, 2015
• Last Update Posted: Jun 29, 2022
• Last Verified: Mar 1, 2022

• Additional relevant MeSH terms: Sarcoma; Gastrointestinal Stromal Tumors; Liposarcoma; Osteosarcoma; Histiocytoma, Malignant Fibrous; Nivolumab; Ipilimumab

Study Results

Participant Flow

Pre-assignment Detail	GIST Cohort: 24 patients assessed for eligibility; 3 excluded (i.e. ineligible) and 21 randomized.> LPS Cohort: 37 patients assessed for eligibility; 11 excluded, 3 included (2 pre-registered as UPS/MFH cohort, 1 pre-registered as GIST cohort) and 29 randomized.> UPS/MFH Cohort: 47 patients assessed for eligibility; 18 excluded and 29 randomized.

Arm/Group Title	Initial Cohort - Arm I (Nivolumab)	Initial Cohort - Arm II (Nivolumab, Ipilimumab)	Expansion LPS Cohort - Arm I (Nivolumab)	Expansion LPS Cohort - Arm II (Nivolumab, Ipilimumab)	Expansion UPS/MFH Cohort - Arm I (Nivolumab)	Expansion UPS/MFH Cohort - Arm II (Nivolumab, Ipilimumab)	Expansion GIST Cohort - Arm I (Nivolumab)	Expansion GIST Cohort - Arm II (Nivolumab, Ipilimumab)
Arm/Group Description	Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress on single agent nivolumab may elect to cross over to Initial Cohort - Arm II.	Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress after 10 weeks on single agent nivolumab may elect to cross over to LPS Cohort - Arm II.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress after 10 weeks on single agent nivolumab may elect to cross over to UPS/MFH Cohort - Arm II.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress after 10 weeks on single agent nivolumab may elect to cross over to GIST Cohort - Arm II.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.
Period Title: Overall Study
STARTED	43	42	15	14	14	15	10	11
Arm I Crossover	4	0	6	0	1	0	2	0
COMPLETED	42	42	15	14	13	14	10	11
NOT COMPLETED	1	0	0	0	1	1	0	0

Baseline Characteristics

Arm/Group Title	Initial Single	Initial Dual	LPS Single	LPS Dual	UPS/MFH Single	UPS/MFH Dual	GIST Single	GIST Dual	Total
Arm/Group Description	Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Total of all reporting groups
Overall Participants	43	42	15	14	14	15	10	11	164
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56.0	57.0	62.0	58.5	63.5	60.0	69.0	62.0	62
Sex: Female, Male (Count of Participants)
Female	21 48.8%	23 54.8%	8 53.3%	5 35.7%	5 35.7%	8 53.3%	2 20%	5 45.5%	77 47%
Male	22 51.2%	19 45.2%	7 46.7%	9 64.3%	9 64.3%	7 46.7%	8 80%	6 54.5%	87 53%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 2.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.6%
Asian	0 0%	1 2.4%	0 0%	0 0%	0 0%	0 0%	1 10%	0 0%	2 1.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	1 7.1%	0 0%	0 0%	0 0%	1 9.1%	2 1.2%
Black or African American	4 9.3%	3 7.1%	0 0%	0 0%	2 14.3%	1 6.7%	2 20%	0 0%	12 7.3%
White	38 88.4%	34 81%	15 100%	13 92.9%	12 85.7%	13 86.7%	7 70%	10 90.9%	142 86.6%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.3%	3 7.1%	0 0%	0 0%	0 0%	1 6.7%	0 0%	0 0%	5 3%
ECOG Performance Status (Count of Participants)
0	28 65.1%	24 57.1%	6 40%	8 57.1%	3 21.4%	7 46.7%	6 60%	8 72.7%	90 54.9%
1	15 34.9%	18 42.9%	9 60%	6 42.9%	11 78.6%	8 53.3%	4 40%	3 27.3%	74 45.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Achieved a Confirmed Response
Description	The number of participants who achieved a confirmed response is defined as the number of patients having a best objective tumor status of complete response (CR) or partial response (PR) lasting at least 4 weeks as determined using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites).
Time Frame	Up to 44 months

Outcome Measure Data

Analysis Population Description

Participants who completed the study and were evaluable for the primary endpoint are included in this analysis.

Arm/Group Title	Initial Single	Initial Dual	LPS Single	LPS Dual	UPS/MFH Single	UPS/MFH Dual	GIST Single	GIST Dual
Arm/Group Description	Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.
Measure Participants	42	42	15	14	13	14	10	11
Count of Participants [Participants]	2 4.7%	6 14.3%	1 6.7%	2 14.3%	1 7.1%	2 13.3%	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants Who Experienced at Least One Grade 3 or Higher Adverse Event Regardless of Attribution
Description	The number of participants who experienced at least one grade 3 or higher adverse event (AE) regardless of attribution. AEs are graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 beginning April 1, 2018).
Time Frame	Up to 4 weeks after completion of study treatment

Outcome Measure Data

Analysis Population Description

Randomized patients who received treatment (i.e. exclude cancel patients).

Arm/Group Title	Initial Single	Initial Dual	LPS Single	LPS Dual	UPS/MFH Single	UPS/MFH Dual	GIST Single	GIST Dual
Arm/Group Description	Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress on single agent nivolumab may elect to cross over to Initial Cohort - Arm II.	Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.
Measure Participants	42	42	15	14	13	14	10	11
Grade 3 Event	19 44.2%	25 59.5%	11 73.3%	5 35.7%	9 64.3%	6 40%	5 50%	6 54.5%
Grade 4 Event	3 7%	4 9.5%	0 0%	0 0%	1 7.1%	2 13.3%	1 10%	1 9.1%
Grade 5 Event	5 11.6%	6 14.3%	1 6.7%	0 0%	3 21.4%	1 6.7%	1 10%	0 0%

3. Secondary Outcome

Title	Duration of Response
Description	Duration of response is defined for all evaluable patients who have achieved a confirmed response as the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression (PD) is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by >= 50% of previously involved sites from nadir).
Time Frame	Time from first response to progression, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

Participants who achieved a confirmed response are included in this analysis.

Arm/Group Title	Initial Single	Initial Dual	LPS Single	LPS Dual	UPS/MFH Single	UPS/MFH Dual	GIST Single	GIST Dual
Arm/Group Description	Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.
Measure Participants	2	6	1	2	1	2	0	0
Median (Full Range) [months]	7.4	6.2	14.5	10.675	14.6	3.19

4. Secondary Outcome

Title	6-Month Clinical Benefit Rate [Initial Cohort]
Description	The 6-month clinical benefit rate is defined as the percentage of participants with a response or stable disease (CR, PR, or SD) at 6 months. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by >= 50% of previously involved sites from nadir, SD: Not CR/PR or PD).
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Randomized Initial Cohort participants who received treatment (i.e. exclude cancel patients) Only.

Arm/Group Title	Initial Single	Initial Dual
Arm/Group Description	Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.
Measure Participants	42	42
Number (90% Confidence Interval) [percentage of participants]	10 23.3%	12 28.6%

5. Secondary Outcome

Title	6-Month Clinical Benefit Rate [Expansion LPS and UPS/MFH Cohorts Only]
Description	The 6-month clinical benefit rate is defined as the percentage of participants with a response or stable disease (CR, PR, or SD) at 6 months. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by >= 50% of previously involved sites from nadir, SD: Not CR/PR or PD).
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Randomized Expansion LPS and UPS/MFH Cohorts Participants who received treatment Only

Arm/Group Title	LPS Single	LPS Dual	UPS/MFH Single	UPS/MFH Dual
Arm/Group Description	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.
Measure Participants	15	14	13	14
Number (85% Confidence Interval) [percentage of participants]	6.7 15.6%	35.7 85%	15.4 102.7%	35.7 255%

6. Secondary Outcome

Title	6-Month Clinical Benefit Rate [Expansion GIST Cohort Only]
Description	The 6-month clinical benefit rate is defined as the percentage of participants with a response or stable disease (CR, PR, or SD) at 6 months. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by >= 50% of previously involved sites from nadir, SD: Not CR/PR or PD).
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Randomized Expansion GIST Cohort Participants who received treatment Only.

Arm/Group Title	GIST Single	GIST Dual
Arm/Group Description	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.
Measure Participants	10	11
Number (80% Confidence Interval) [percentage of participants]	10 23.3%	54.5 129.8%

7. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression (PD) is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. (PD: Any new lesion or increase by >= 50% of previously involved sites from nadir).
Time Frame	Time from randomization to first of either disease progression or death from any cause, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Initial Single	Initial Dual	LPS Single	LPS Dual	UPS/MFH Single	UPS/MFH Dual	GIST Single	GIST Dual
Arm/Group Description	Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.
Measure Participants	42	41	15	14	13	14	10	11
Median (95% Confidence Interval) [months]	1.7	4.1	4.6	5.5	1.5	2.7	1.5	2.9

8. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time Frame	Time from randomization to death from any cause, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Initial Single	Initial Dual	LPS Single	LPS Dual	UPS/MFH Single	UPS/MFH Dual	GIST Single	GIST Dual
Arm/Group Description	Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.	Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.
Measure Participants	42	41	15	14	13	14	10	11
Median (95% Confidence Interval) [months]	10.7	14.3	8.1	13.1	6.6	NA	9.1	12.2

9. Other Pre-specified Outcome

Title	PD-L1 Expression Assessed Using Immunohistochemistry (IHC)
Description	Categorical data analysis and logistic regression will be used to evaluate the associations between PD-L1 expression (by IHC) and clinical outcome (e.g., response, clinical benefit, progression-free survival, and survival). Kaplan-Meier methodology and Cox proportional hazards models will be used to evaluate time to event endpoints.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Change in Selected Biomarkers Measured in Serial Peripheral Blood
Description	Summary statistics will be used to for describing changes across time. The time course of biomarker outcomes will be investigated graphically, by summary plots or individual patient plots. If there is suggestion of meaningful trend, methods such as linear mixed models may be used to characterize the pattern of change over time. Kaplan-Meier methodology and Cox proportional hazards models will be used to evaluate time to event endpoints.
Time Frame	Baseline to up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Other Pre-specified Outcome

Title	Selected Biomarkers Measured in Tumor Tissue
Description	Categorical data analysis and logistic regression will be used to correlated biomarkers with and clinical outcome (e.g., response, clinical benefit, time to progression, progression free survival, and survival) within each study component. Kaplan-Meier methodology and Cox proportional hazards models will be used to evaluate time to event endpoints.
Time Frame	Up to week 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Other Pre-specified Outcome

Title	Confirmed Response in Patients Who Crossover From Single Agent Nivolumab to Dual Agent Treatment Following Progression
Description	Confirmed response will be evaluated in patients who crossover from single agent nivolumab to dual agent treatment following progression.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Other Pre-specified Outcome

Title	Duration of Response in Patients Who Crossover From Single Agent Nivolumab to Dual Agent Treatment Following Progression
Description	Evaluated using Kaplan-Meier methodology.
Time Frame	Time from first response to progression, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Other Pre-specified Outcome

Title	PFS in Patients Who Crossover From Single Agent Nivolumab to Dual Agent Treatment Following Progression
Description	Evaluated using Kaplan-Meier methodology.
Time Frame	Time from randomization to first of either disease progression or death from any cause, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Other Pre-specified Outcome

Title	OS in Patients Who Crossover From Single Agent Nivolumab to Dual Agent Treatment Following Progression
Description	Evaluated using Kaplan-Meier methodology.
Time Frame	Time from randomization to death from any cause, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to 4 weeks after completion of study treatment; up to 44 months
Adverse Event Reporting Description	Serious AEs and Other (Not Including Serious) AEs summary tables summarizes AEs assessed for participants who started treatment and were evaluable for AEs. All-cause mortality is assessed for all enrolled participants. Adverse events are described and graded using the terminology and grading categories defined in the NCI's Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0. However, CTCAE v5.0 is used for serious AE reporting through CTEP-AERS as of April 1, 2018.
Arm/Group Title	Initial Single		Initial Dual		LPS Single		LPS Dual		UPS/MFH Single		UPS/MFH Dual		GIST Single		GIST Dual
Arm/Group Description	Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.		Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.		Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.		Dedifferentiated liposarcoma (LPS) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.		Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.		Undifferentiated Pleomorphic Sarcoma & Malignant Fibrous Histiocytoma (UPS/MFH) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.		Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes once every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity.		Gastrointestinal stromal tumor (GIST) Cohort Patients receive 3mg/kg nivolumab IV over 30 minutes and 1mg/kg ipilimumab IV over 90 minutes once every 3 weeks for 12 weeks. Patients then receive 3mg/kg nivolumab IV over 30 minutes every 2 weeks. Cycles repeat every 42 days for up to 108 weeks in the absence of disease progression or unacceptable toxicity. Patients who progress by imaging during the first 12 weeks of therapy may continue treatment, at the discretion of the patient and treating investigator.
All Cause Mortality
	Initial Single		Initial Dual		LPS Single		LPS Dual		UPS/MFH Single		UPS/MFH Dual		GIST Single		GIST Dual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/43 (86%)		34/42 (81%)		11/15 (73.3%)		10/14 (71.4%)		10/14 (71.4%)		7/15 (46.7%)		8/10 (80%)		7/11 (63.6%)
Serious Adverse Events
	Initial Single		Initial Dual		LPS Single		LPS Dual		UPS/MFH Single		UPS/MFH Dual		GIST Single		GIST Dual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/42 (45.2%)		21/42 (50%)		9/15 (60%)		1/14 (7.1%)		8/13 (61.5%)		7/14 (50%)		5/10 (50%)		6/11 (54.5%)
Blood and lymphatic system disorders
Anemia	4/42 (9.5%)	5	5/42 (11.9%)	5	2/15 (13.3%)	2	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Febrile neutropenia	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Endocrine disorders
Adrenal insufficiency	0/42 (0%)	0	3/42 (7.1%)	3	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Eye disorders
Papilledema	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Gastrointestinal disorders
Abdominal pain	3/42 (7.1%)	4	2/42 (4.8%)	2	0/15 (0%)	0	1/14 (7.1%)	1	1/13 (7.7%)	1	1/14 (7.1%)	1	0/10 (0%)	0	1/11 (9.1%)	1
Ascites	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Colitis	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Colonic perforation	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Constipation	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Diarrhea	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	3/11 (27.3%)	3
Ileus	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Jejunal obstruction	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Lower gastrointestinal hemorrhage	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Nausea	2/42 (4.8%)	2	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Obstruction gastric	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	2	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Rectal obstruction	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Small intestinal obstruction	1/42 (2.4%)	3	1/42 (2.4%)	2	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Vomiting	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	1
General disorders
Chills	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Death NOS	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Edema limbs	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Fatigue	0/42 (0%)	0	3/42 (7.1%)	3	2/15 (13.3%)	2	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Fever	2/42 (4.8%)	2	1/42 (2.4%)	1	1/15 (6.7%)	1	0/14 (0%)	0	2/13 (15.4%)	2	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Localized edema	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Pain	1/42 (2.4%)	1	2/42 (4.8%)	2	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Sudden death NOS	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Infections and infestations
Abdominal infection	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Infections and infestations - Oth spec	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Lung infection	1/42 (2.4%)	1	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Sepsis	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Skin infection	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Upper respiratory infection	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Urinary tract infection	1/42 (2.4%)	1	3/42 (7.1%)	3	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Wound infection	0/42 (0%)	0	2/42 (4.8%)	2	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Injury, poisoning and procedural complications
Fall	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	1/11 (9.1%)	1
Intraoperative urinary injury	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Spinal fracture	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Investigations
Alanine aminotransferase increased	0/42 (0%)	0	2/42 (4.8%)	2	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Alkaline phosphatase increased	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Aspartate aminotransferase increased	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Creatinine increased	2/42 (4.8%)	2	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Lipase increased	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Lymphocyte count decreased	1/42 (2.4%)	1	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Lymphocyte count increased	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Platelet count decreased	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Urine output decreased	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Metabolism and nutrition disorders
Anorexia	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Dehydration	2/42 (4.8%)	2	1/42 (2.4%)	2	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Hyperglycemia	1/42 (2.4%)	1	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Hyperkalemia	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Hypoalbuminemia	1/42 (2.4%)	1	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Hypokalemia	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Hyponatremia	0/42 (0%)	0	4/42 (9.5%)	4	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Hypophosphatemia	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	2	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Generalized muscle weakness	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Myalgia	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, mal, uncpec - Oth spec	2/42 (4.8%)	2	2/42 (4.8%)	2	1/15 (6.7%)	1	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Tumor pain	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Nervous system disorders
Cognitive disturbance	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Encephalopathy	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Intracranial hemorrhage	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Nervous system disorders - Oth spec	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Seizure	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/42 (2.4%)	1	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Renal and urinary disorders - Oth spec	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Urinary tract obstruction	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Reproductive system and breast disorders
Vaginal fistula	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Cough	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Dyspnea	0/42 (0%)	0	2/42 (4.8%)	2	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Pleural effusion	3/42 (7.1%)	3	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Productive cough	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Pulmonary edema	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Respiratory failure	2/42 (4.8%)	2	2/42 (4.8%)	2	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Urticaria	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Surgical and medical procedures
Surgical and medical proced - Oth spec	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Vascular disorders
Hematoma	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Hypotension	0/42 (0%)	0	3/42 (7.1%)	4	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Thromboembolic event	1/42 (2.4%)	1	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	Initial Single		Initial Dual		LPS Single		LPS Dual		UPS/MFH Single		UPS/MFH Dual		GIST Single		GIST Dual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/42 (92.9%)		40/42 (95.2%)		15/15 (100%)		14/14 (100%)		12/13 (92.3%)		14/14 (100%)		10/10 (100%)		10/11 (90.9%)
Blood and lymphatic system disorders
Anemia	10/42 (23.8%)	13	10/42 (23.8%)	16	3/15 (20%)	5	3/14 (21.4%)	6	2/13 (15.4%)	3	3/14 (21.4%)	7	1/10 (10%)	1	1/11 (9.1%)	1
Leukocytosis	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Thrombotic thrombocytopenic purpura	2/42 (4.8%)	13	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Cardiac disorders
Cardiac disorders - Other, specify	0/42 (0%)	0	2/42 (4.8%)	5	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Palpitations	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Paroxysmal atrial tachycardia	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	2	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Pericardial effusion	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Sinus tachycardia	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	2	1/14 (7.1%)	1	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Ear and labyrinth disorders
Ear and labyrinth disorders - Oth spec	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
External ear inflammation	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Endocrine disorders
Adrenal insufficiency	0/42 (0%)	0	3/42 (7.1%)	7	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Endocrine disorders - Other, specify	0/42 (0%)	0	1/42 (2.4%)	3	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	8	0/11 (0%)	0
Hyperthyroidism	1/42 (2.4%)	1	0/42 (0%)	0	1/15 (6.7%)	8	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	1/10 (10%)	2	1/11 (9.1%)	1
Hypothyroidism	6/42 (14.3%)	10	7/42 (16.7%)	28	3/15 (20%)	6	2/14 (14.3%)	4	1/13 (7.7%)	1	4/14 (28.6%)	14	1/10 (10%)	9	2/11 (18.2%)	8
Eye disorders
Blurred vision	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	2/14 (14.3%)	6	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Dry eye	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Watering eyes	1/42 (2.4%)	2	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Gastrointestinal disorders
Abdominal distension	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Abdominal pain	11/42 (26.2%)	21	11/42 (26.2%)	19	9/15 (60%)	20	8/14 (57.1%)	18	1/13 (7.7%)	2	1/14 (7.1%)	7	7/10 (70%)	9	8/11 (72.7%)	22
Bloating	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Colitis	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Constipation	5/42 (11.9%)	8	6/42 (14.3%)	13	1/15 (6.7%)	1	1/14 (7.1%)	1	1/13 (7.7%)	1	2/14 (14.3%)	2	1/10 (10%)	1	1/11 (9.1%)	1
Diarrhea	4/42 (9.5%)	6	13/42 (31%)	15	6/15 (40%)	13	6/14 (42.9%)	9	3/13 (23.1%)	4	5/14 (35.7%)	5	2/10 (20%)	4	6/11 (54.5%)	15
Dry mouth	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	6	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	1/10 (10%)	1	1/11 (9.1%)	1
Flatulence	1/42 (2.4%)	3	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Gastritis	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Gastroesophageal reflux disease	1/42 (2.4%)	3	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Gastrointestinal fistula	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Hemorrhoids	0/42 (0%)	0	2/42 (4.8%)	2	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Ileus	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Lower gastrointestinal hemorrhage	1/42 (2.4%)	2	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Mucositis oral	0/42 (0%)	0	2/42 (4.8%)	2	1/15 (6.7%)	2	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Nausea	11/42 (26.2%)	17	12/42 (28.6%)	18	7/15 (46.7%)	12	5/14 (35.7%)	11	2/13 (15.4%)	4	5/14 (35.7%)	10	3/10 (30%)	10	6/11 (54.5%)	9
Small intestinal obstruction	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Vomiting	2/42 (4.8%)	4	2/42 (4.8%)	2	1/15 (6.7%)	2	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	6	1/11 (9.1%)	1
General disorders
Edema limbs	1/42 (2.4%)	1	1/42 (2.4%)	1	1/15 (6.7%)	1	0/14 (0%)	0	1/13 (7.7%)	1	3/14 (21.4%)	4	0/10 (0%)	0	2/11 (18.2%)	7
Edema trunk	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Fatigue	27/42 (64.3%)	58	29/42 (69%)	71	12/15 (80%)	27	13/14 (92.9%)	43	9/13 (69.2%)	14	11/14 (78.6%)	32	9/10 (90%)	14	6/11 (54.5%)	23
Fever	3/42 (7.1%)	3	2/42 (4.8%)	2	3/15 (20%)	3	1/14 (7.1%)	1	0/13 (0%)	0	3/14 (21.4%)	4	0/10 (0%)	0	0/11 (0%)	0
Flu like symptoms	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Gait disturbance	1/42 (2.4%)	3	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Gen disord and admin site conds-Oth spec	1/42 (2.4%)	3	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Localized edema	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Malaise	0/42 (0%)	0	1/42 (2.4%)	2	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Non-cardiac chest pain	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Pain	3/42 (7.1%)	6	2/42 (4.8%)	6	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Immune system disorders
Allergic reaction	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Infections and infestations
Conjunctivitis	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	2	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Gum infection	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Infections and infestations - Oth spec	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Papulopustular rash	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Pleural infection	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Rash pustular	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Sinusitis	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	2	0/10 (0%)	0	0/11 (0%)	0
Skin infection	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	1/14 (7.1%)	1	1/13 (7.7%)	1	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Upper respiratory infection	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Urinary tract infection	0/42 (0%)	0	1/42 (2.4%)	1	2/15 (13.3%)	2	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Wound infection	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Injury, poisoning and procedural complications
Infusion related reaction	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Wrist fracture	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Investigations
Alanine aminotransferase increased	3/42 (7.1%)	5	3/42 (7.1%)	3	0/15 (0%)	0	2/14 (14.3%)	2	1/13 (7.7%)	2	3/14 (21.4%)	4	1/10 (10%)	1	1/11 (9.1%)	1
Alkaline phosphatase increased	2/42 (4.8%)	4	3/42 (7.1%)	4	2/15 (13.3%)	2	4/14 (28.6%)	7	0/13 (0%)	0	1/14 (7.1%)	2	1/10 (10%)	7	1/11 (9.1%)	1
Aspartate aminotransferase increased	1/42 (2.4%)	1	4/42 (9.5%)	4	0/15 (0%)	0	1/14 (7.1%)	1	1/13 (7.7%)	2	4/14 (28.6%)	5	2/10 (20%)	9	0/11 (0%)	0
Blood bilirubin increased	2/42 (4.8%)	2	1/42 (2.4%)	4	0/15 (0%)	0	2/14 (14.3%)	2	0/13 (0%)	0	1/14 (7.1%)	2	3/10 (30%)	8	2/11 (18.2%)	3
Creatinine increased	1/42 (2.4%)	1	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	3
GGT increased	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Investigations - Other, specify	0/42 (0%)	0	1/42 (2.4%)	3	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Lipase increased	2/42 (4.8%)	2	3/42 (7.1%)	3	1/15 (6.7%)	1	1/14 (7.1%)	2	0/13 (0%)	0	2/14 (14.3%)	2	1/10 (10%)	1	2/11 (18.2%)	2
Lymphocyte count decreased	5/42 (11.9%)	7	3/42 (7.1%)	3	4/15 (26.7%)	10	1/14 (7.1%)	2	1/13 (7.7%)	1	2/14 (14.3%)	2	1/10 (10%)	3	1/11 (9.1%)	1
Lymphocyte count increased	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Neutrophil count decreased	0/42 (0%)	0	1/42 (2.4%)	4	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	2/14 (14.3%)	4	0/10 (0%)	0	0/11 (0%)	0
Platelet count decreased	2/42 (4.8%)	2	1/42 (2.4%)	1	2/15 (13.3%)	2	1/14 (7.1%)	2	1/13 (7.7%)	1	1/14 (7.1%)	2	1/10 (10%)	3	0/11 (0%)	0
Weight loss	0/42 (0%)	0	1/42 (2.4%)	1	1/15 (6.7%)	1	1/14 (7.1%)	1	0/13 (0%)	0	3/14 (21.4%)	6	1/10 (10%)	3	0/11 (0%)	0
White blood cell decreased	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Metabolism and nutrition disorders
Anorexia	12/42 (28.6%)	18	14/42 (33.3%)	21	10/15 (66.7%)	20	3/14 (21.4%)	4	5/13 (38.5%)	7	7/14 (50%)	8	5/10 (50%)	7	5/11 (45.5%)	11
Dehydration	0/42 (0%)	0	2/42 (4.8%)	2	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Hyperglycemia	0/42 (0%)	0	3/42 (7.1%)	10	3/15 (20%)	4	1/14 (7.1%)	1	0/13 (0%)	0	2/14 (14.3%)	4	1/10 (10%)	1	0/11 (0%)	0
Hyperkalemia	0/42 (0%)	0	2/42 (4.8%)	2	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Hypernatremia	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	2	0/11 (0%)	0
Hyperuricemia	1/42 (2.4%)	2	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Hypoalbuminemia	2/42 (4.8%)	4	3/42 (7.1%)	4	3/15 (20%)	4	2/14 (14.3%)	2	0/13 (0%)	0	3/14 (21.4%)	5	0/10 (0%)	0	0/11 (0%)	0
Hypocalcemia	2/42 (4.8%)	6	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Hypoglycemia	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Hypokalemia	1/42 (2.4%)	1	3/42 (7.1%)	4	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	3	1/11 (9.1%)	1
Hypomagnesemia	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Hyponatremia	3/42 (7.1%)	3	2/42 (4.8%)	3	4/15 (26.7%)	6	1/14 (7.1%)	2	1/13 (7.7%)	1	3/14 (21.4%)	3	1/10 (10%)	2	2/11 (18.2%)	2
Hypophosphatemia	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	8/42 (19%)	16	8/42 (19%)	17	3/15 (20%)	5	6/14 (42.9%)	18	9/13 (69.2%)	12	6/14 (42.9%)	15	5/10 (50%)	5	4/11 (36.4%)	6
Back pain	0/42 (0%)	0	2/42 (4.8%)	2	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	1/14 (7.1%)	1	0/10 (0%)	0	1/11 (9.1%)	1
Chest wall pain	1/42 (2.4%)	2	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Generalized muscle weakness	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	2	1/14 (7.1%)	1	1/10 (10%)	1	0/11 (0%)	0
Myalgia	3/42 (7.1%)	3	2/42 (4.8%)	3	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Myositis	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Neck pain	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Pain in extremity	2/42 (4.8%)	2	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	2/14 (14.3%)	2	0/10 (0%)	0	0/11 (0%)	0
Nervous system disorders
Dizziness	1/42 (2.4%)	2	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Dysgeusia	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	2	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	1
Headache	2/42 (4.8%)	2	0/42 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	2	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Nervous system disorders - Oth spec	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Peripheral motor neuropathy	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Peripheral sensory neuropathy	1/42 (2.4%)	1	2/42 (4.8%)	2	2/15 (13.3%)	3	0/14 (0%)	0	2/13 (15.4%)	3	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Psychiatric disorders
Anxiety	3/42 (7.1%)	6	1/42 (2.4%)	1	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	1/11 (9.1%)	1
Depression	1/42 (2.4%)	2	2/42 (4.8%)	3	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Insomnia	2/42 (4.8%)	4	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Renal and urinary disorders
Hematuria	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	2	0/11 (0%)	0
Proteinuria	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Renal calculi	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Urinary frequency	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	2
Urinary tract obstruction	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	1/10 (10%)	1	0/11 (0%)	0
Urinary tract pain	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Reproductive system and breast disorders
Genital edema	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Cough	14/42 (33.3%)	17	8/42 (19%)	24	7/15 (46.7%)	11	6/14 (42.9%)	13	7/13 (53.8%)	10	5/14 (35.7%)	9	3/10 (30%)	7	3/11 (27.3%)	15
Dyspnea	10/42 (23.8%)	19	10/42 (23.8%)	17	4/15 (26.7%)	5	3/14 (21.4%)	4	8/13 (61.5%)	14	2/14 (14.3%)	5	4/10 (40%)	6	3/11 (27.3%)	16
Epistaxis	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Hoarseness	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1
Hypoxia	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Nasal congestion	2/42 (4.8%)	3	2/42 (4.8%)	3	1/15 (6.7%)	2	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	3	0/10 (0%)	0	1/11 (9.1%)	1
Pleural effusion	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	5	0/10 (0%)	0	0/11 (0%)	0
Pleuritic pain	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0
Pneumonitis	1/42 (2.4%)	2	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Pulmonary edema	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	1/42 (2.4%)	1	0/42 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Dry skin	0/42 (0%)	0	1/42 (2.4%)	3	2/15 (13.3%)	11	1/14 (7.1%)	1	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Nail ridging	0/42 (0%)	0	0/42 (0%)	0	1/15 (6.7%)	2	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Pruritus	2/42 (4.8%)	2	4/42 (9.5%)	5	3/15 (20%)	7	3/14 (21.4%)	10	4/13 (30.8%)	17	0/14 (0%)	0	1/10 (10%)	2	2/11 (18.2%)	14
Purpura	0/42 (0%)	0	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Rash acneiform	1/42 (2.4%)	1	0/42 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	2	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	1/11 (9.1%)	1
Rash maculo-papular	5/42 (11.9%)	7	4/42 (9.5%)	5	2/15 (13.3%)	5	2/14 (14.3%)	4	2/13 (15.4%)	3	1/14 (7.1%)	1	2/10 (20%)	4	0/11 (0%)	0
Skin and subcut tissue disord - Oth spec	0/42 (0%)	0	2/42 (4.8%)	2	1/15 (6.7%)	2	0/14 (0%)	0	2/13 (15.4%)	10	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Skin ulceration	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Urticaria	0/42 (0%)	0	1/42 (2.4%)	2	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Surgical and medical procedures
Surgical and medical proced - Oth spec	0/42 (0%)	0	0/42 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/13 (7.7%)	1	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Vascular disorders
Hypertension	0/42 (0%)	0	2/42 (4.8%)	2	3/15 (20%)	6	1/14 (7.1%)	2	2/13 (15.4%)	2	0/14 (0%)	0	1/10 (10%)	6	0/11 (0%)	0
Hypotension	1/42 (2.4%)	1	2/42 (4.8%)	2	1/15 (6.7%)	1	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Lymphedema	1/42 (2.4%)	2	1/42 (2.4%)	1	0/15 (0%)	0	0/14 (0%)	0	0/13 (0%)	0	0/14 (0%)	0	0/10 (0%)	0	0/11 (0%)	0
Thromboembolic event	1/42 (2.4%)	1	2/42 (4.8%)	5	0/15 (0%)	0	1/14 (7.1%)	1	0/13 (0%)	0	1/14 (7.1%)	1	0/10 (0%)	0	0/11 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.