MEDI4736 (Durvalumab) in Patients With Brain Metastasis From Epithelial-derived Tumors

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02669914
• Collaborator: AstraZeneca (Industry)
• Enrollment: 4
• Location: 1
• Arms: 3
• Actual Duration (Months): 16
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Brain metastases are the most common intracranial malignancy occurring in 20-40% of all cancers, and the presence of CNS metastases is associated with a poor prognosis. As such, the median overall survival of patients with symptomatic brain lesions is a dismal 2-3 months regardless of tumor type. Because standard chemotherapy largely does not cross the blood brain barrier at a meaningful concentration, standard treatment is limited and usually involves surgical resection and/or stereotactic radiosurgery for isolated lesions and whole brain radiation for multiple lesions. Unfortunately, the median overall survival is only improved by about 6 months with this multimodality approach2, and there is a paucity of second-line therapies to treat recurrence. Furthermore, re-resection and re-radiation are often not feasible options due to concern for increasing complications or neurotoxicity, respectively. Thus, there is a dire clinical need for additional treatment options for this patient population.

Checkpoint blockade therapy, in particular PD-1 and PD-L1 inhibition, has recently shown clinical efficacy in multiple types of solid tumors. The investigators propose to study the efficacy of checkpoint blockade therapy in patients with solid tumors and refractory/recurrent brain metastases. The investigators will assess the efficacy of MEDI4736, a novel PD-L1 inhibitory monoclonal antibody, in this study.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer; Nonsmall Cell Lung Cancer; Breast Cancer; Cancer of Breast; Cancer of the Breast; Gastroesophageal Cancer; Pancreatic Cancer; Cancer of the Pancreas; Colorectal Cancer; Colorectal Carcinoma; Renal Cancer; Kidney Cancer; Cancer of the Kidney; Cancer of Kidney; Ovarian Cancer; Ovary Cancer; Cancer of the Ovary; Cancer of Ovary	Drug: MEDI4736	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of MEDI4736 (Durvalumab) in Patients With Brain Metastasis From Epithelial-derived Tumors
• Actual Study Start Date: Sep 12, 2016
• Actual Primary Completion Date: Sep 21, 2017
• Actual Study Completion Date: Jan 11, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: Non-small cell lung cancer w/o corticosteroids -MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	Drug: MEDI4736; Other Names: Durvalumab
Experimental: Cohort B: Epithelial origin solid tumors w/o corticosteroids -MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	Drug: MEDI4736; Other Names: Durvalumab
Experimental: Cohort C: NSCLC or non-NSCLC w/corticosteroids -MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	Drug: MEDI4736; Other Names: Durvalumab

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate of Intracranial Disease [Completion of treatment (estimated to be 6 months)]

   -% of subjects who achieve a complete response (CR) or partial response (CR) based on assessment of brain lesions CR: Requires: complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; No new lesions; stable or improved nonenhancing (T2/FLAIR) lesions.; off corticosteroids (or on physiologic replacement doses only) and stable or improved clinically. PR: Requires:• ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. • No progression of nonmeasurable disease. • Stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at time of baseline scan. • Stable or improved clinically

Secondary Outcome Measures

1. Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events [30 days after completion of treatment (estimated to be 7 months)]

   -The severity of AEs will be graded by the investigator according to the CTCAE, Version 4.03

2. Overall Disease Control Rate of Intracranial Disease [Completion of treatment (estimated to be 6 months)]

   Defined as the percentage of patients who achieve a complete response, partial response, or stable disease based on assessment of brain lesions CR: Requires: complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; No new lesions; stable or improved nonenhancing (T2/FLAIR) lesions.; off corticosteroids (or on physiologic replacement doses only) and stable or improved clinically. PR: Requires:• ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. • No progression of nonmeasurable disease. • Stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at time of baseline scan. • Stable or improved clinically

3. Overall Response Rate of Extracranial Disease [Completion of treatment (estimated to be 6 months)]

   Defined as the percentage of patients who achieve a complete response or partial response based on assessment of systemic lesions Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters

4. Overall Disease Control Rate of Extracranial Disease [Completion of treatment (estimated to be 6 months)]

   Defined as the percentage of patients who achieve a complete response, partial response, or stable disease based on assessment of systemic lesions Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Stable disease: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study

5. Overall Response Rate Considering Both Intracranial and Extracranial Disease [Completion of treatment (estimated to be 6 months)]

   Defined as the percentage of patients who achieve a complete response or partial response based on assessment of brain and systemic lesions Intracranial disease Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Extracranial disease Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters

6. Overall Disease Control Rate Considering Both Intracranial and Extracranial Disease [Completion of treatment (estimated to be 6 months)]

   Defined as the percentage of subjects who achieve a complete response, partial response, or stable disease based on assessment of brain and systemic lesions Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

7. Duration of Response of Intracranial Disease [Completion of treatment (estimated to be 6 months)]

   Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline

8. Duration of Response of Extracranial Disease [Completion of treatment (estimated to be 6 months)]

   Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

9. Duration of Response Considering Both Intracranial and Extracranial Disease [Completion of treatment (estimated to be 6 months)]

   Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

10. Progression-free Survival (PFS) [Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)]

    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Unequivocal progression of existing non-target lesions.

11. Overall Survival (OS) [Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)]

    -Defined as the interval from the start of study therapy to death from any cause

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Cohort A: Histologically confirmed metastatic non-small cell lung cancer (all histologic subtypes allowed) with radiographic evidence by MRI of at least one measurable brain lesion as defined by RANO criteria that does not require corticosteroids for symptomatic control.

• Cohort B: Histologically confirmed metastatic solid tumor of epithelial origin, excluding NSCLC, including but not limited to ovarian cancer, colorectal cancer, pancreatic cancer, gastric cancer, renal cancer, bladder cancer, or breast cancer with radiographic evidence by MRI of at least one measurable brain lesion as defined by RANO criteria that does not require corticosteroids for symptomatic control.

• Cohort C: Histologically confirmed metastatic solid tumor of epithelial origin, including both NSCLC and non-NSCLC, with radiographic evidence by MRI of at least one measurable brain lesion as defined by RANO criteria that requires corticosteroids for symptomatic control.

• At least one prior treatment to a CNS-based lesion is required. Prior therapy must be completed > 2 weeks prior to enrollment. A previously treated lesion must be demonstrated by MRI to have progressed following treatment in order to be eligible. The subsequent development of a new CNS lesion that was not previously treated will be permitted and dose not require treatment followed by progression prior to enrollment. Treatment of a single CNS lesion with local therapy in the context of multifocal disease is permitted as long as at least one untreated lesions meets criteria for measurable disease. Patients should have received minimum of one line of systemic therapy.

• At least 18 years of age.

• ECOG performance status of 0 to 2

• Adequate bone marrow and organ function as defined below:

• Absolute neutrophil count ≥ 1,500/mcL

• Platelets ≥ 100,000/mcL

• Hemoglobin ≥ 8.0 g/dL

• Serum bilirubin ≤ 1.5 x IULN

• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN

• Creatinine clearance ≥ 40 mL/min/1.73 m2 by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance

• Negative antiviral serology:

• Negative human immunodeficiency virus (HIV) antibody.

• Negative hepatitis B surface antigen (HBsAg) and negative hepatitis B core (HBc) antibody or undetectable hepatitis B (HBV) DNA by quantitative polymerase chain reaction (PCR) testing.

• Negative hepatitis C virus (HCV) antibody or negative HCV ribonucleic acid (RNA) by quantitative PCR.

• Mean QT interval corrected for heart rate (QTc) < 470 msec calculated from 3 ECGs performed at least 2 minutes apart using Frediricia's Correction.

• Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥60 years old and no menses for 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.

• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Diagnosis of leptomeningeal carcinomatosis.

• Diagnosis of melanoma or other non-epithelial based malignancy such as sarcoma, neuroendocrine tumor, small cell lung cancer.

• Presence of unstable systemic disease (e.g., visceral crisis or rapid progression) in the judgment of the investigator.

• A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.

• Currently receiving any other investigational agents.

• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEDI4736 or other agents used in the study.

• Previous treatment with a PD-1 or PD-L1 inhibitor, including MEDI4736, or a CTLA-4 inhibitory agent.

• Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736 with the exceptions of intranasal and inhaled corticosteroids, or systemic corticosteroids in Cohort C.

• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 21 days prior to the first dose of study drug.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension (>180/110), unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements.

• Active or prior documented autoimmune disease within the past 2 years (Note: subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded).

• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).

• History of prior immunodeficiency.

• History of allogeneic organ transplant.

• Known history of previous clinical diagnosis of tuberculosis.

• Receipt of live attenuated vaccination within 30 days prior to first dose of MEDI4736.

• Pregnant and/or breastfeeding or female patients of reproductive potential who are not employing an effective method of birth control.

• Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• AstraZeneca

Investigators

• Principal Investigator: Ramaswamy Govindan, M.D., Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 23, 2016

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT02669914
• Other Study ID Numbers: 201602169
• First Posted: Feb 1, 2016
• Last Update Posted: Nov 6, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Pancreatic Neoplasms; Ovarian Neoplasms; Brain Neoplasms; Kidney Neoplasms; Carcinoma, Renal Cell; Breast Neoplasms; Durvalumab

Study Results

Participant Flow

Recruitment Details	The study opened to participant enrollment on 09/12/2016 and closed to participant accrual on 11/16/2017.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Period Title: Overall Study
STARTED	4	0	0
COMPLETED	4	0	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids	Total
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	Total of all reporting groups
Overall Participants	4	0	0	4
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	62
Sex: Female, Male (Count of Participants)
Female	3 75%	3 Infinity
Male	1 25%	1 Infinity
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 NaN
Not Hispanic or Latino	4 100%	4 Infinity
Unknown or Not Reported	0 0%	0 NaN
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN
Asian	0 0%	0 NaN
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN
Black or African American	1 25%	1 Infinity
White	3 75%	3 Infinity
More than one race	0 0%	0 NaN
Unknown or Not Reported	0 0%	0 NaN
Region of Enrollment (Count of Participants)
United States	4 100%	4 Infinity

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate of Intracranial Disease
Description	-% of subjects who achieve a complete response (CR) or partial response (CR) based on assessment of brain lesions CR: Requires: complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; No new lesions; stable or improved nonenhancing (T2/FLAIR) lesions.; off corticosteroids (or on physiologic replacement doses only) and stable or improved clinically. PR: Requires:• ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. • No progression of nonmeasurable disease. • Stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at time of baseline scan. • Stable or improved clinically
Time Frame	Completion of treatment (estimated to be 6 months)

Outcome Measure Data

Analysis Population Description

There were not any participants enrolled in Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	4	0	0
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Safety of MEDI4736 in Advanced Solid Epithelial-derived Tumor Patients With Brain Metastases as Measured by Number of Participants With Treatment-emergent Adverse Events
Description	-The severity of AEs will be graded by the investigator according to the CTCAE, Version 4.03
Time Frame	30 days after completion of treatment (estimated to be 7 months)

Outcome Measure Data

Analysis Population Description

There were not any participants enrolled in Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	4	0	0
Grade 1 anemia	1 25%
Grade 2 anemia	1 25%
Grade 1 bloating	1 25%
Grade 2 constipation	1 25%
Grade 2 diarrhea	1 25%
Grade 1 nausea	1 25%
Grade 1 chills	1 25%
Grade 2 fever	1 25%
Grade 1 non-cardiac chest pain	1 25%
Grade 1 night sweats	1 25%
Grade 2 sinusitis	1 25%
Grade 1 lymphocyte count decreased	1 25%
Grade 2 lymphocyte count decreased	2 50%
Grade 2 weight loss	1 25%
Grade 1 hypercalcemia	1 25%
Grade 3 hypercalcemia	1 25%
Grade 1 hyponatremia	1 25%
Grade 1 arthralgia	1 25%
Grade 3 paresthesia	1 25%
Grade 1 productive cough	1 25%
Grade 2 post nasal drip	1 25%
Grade 1 hyperhidrosis	1 25%
Grade 1 pruritus	1 25%
Grade 1 hypertension	1 25%

3. Secondary Outcome

Title	Overall Disease Control Rate of Intracranial Disease
Description	Defined as the percentage of patients who achieve a complete response, partial response, or stable disease based on assessment of brain lesions CR: Requires: complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; No new lesions; stable or improved nonenhancing (T2/FLAIR) lesions.; off corticosteroids (or on physiologic replacement doses only) and stable or improved clinically. PR: Requires:• ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks. • No progression of nonmeasurable disease. • Stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at time of baseline scan. • Stable or improved clinically
Time Frame	Completion of treatment (estimated to be 6 months)

Outcome Measure Data

Analysis Population Description

There were not any participants enrolled in Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	4	0	0
Count of Participants [Participants]	2 50%

4. Secondary Outcome

Title	Overall Response Rate of Extracranial Disease
Description	Defined as the percentage of patients who achieve a complete response or partial response based on assessment of systemic lesions Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters
Time Frame	Completion of treatment (estimated to be 6 months)

Outcome Measure Data

Analysis Population Description

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. There were not any participants enrolled in Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	2	0	0
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Overall Disease Control Rate of Extracranial Disease
Description	Defined as the percentage of patients who achieve a complete response, partial response, or stable disease based on assessment of systemic lesions Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Stable disease: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study
Time Frame	Completion of treatment (estimated to be 6 months)

Outcome Measure Data

Analysis Population Description

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. There were not any participants enrolled in Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	2	0	0
Count of Participants [Participants]	1 25%

6. Secondary Outcome

Title	Overall Response Rate Considering Both Intracranial and Extracranial Disease
Description	Defined as the percentage of patients who achieve a complete response or partial response based on assessment of brain and systemic lesions Intracranial disease Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters Extracranial disease Complete response: Disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters
Time Frame	Completion of treatment (estimated to be 6 months)

Outcome Measure Data

Analysis Population Description

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. There were not any participants enrolled in Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	2	0	0
Count of Participants [Participants]	0 0%

7. Secondary Outcome

Title	Overall Disease Control Rate Considering Both Intracranial and Extracranial Disease
Description	Defined as the percentage of subjects who achieve a complete response, partial response, or stable disease based on assessment of brain and systemic lesions Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Time Frame	Completion of treatment (estimated to be 6 months)

Outcome Measure Data

Analysis Population Description

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. There were not any participants enrolled in Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	2	0	0
Count of Participants [Participants]	1 25%

8. Secondary Outcome

Title	Duration of Response of Intracranial Disease
Description	Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline
Time Frame	Completion of treatment (estimated to be 6 months)

Outcome Measure Data

Analysis Population Description

None of the participants in Cohort A were evaluable for this outcome measure as they did not have an objective response per RANO guidelines. There were not any participants enrolled to Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	0	0	0

9. Secondary Outcome

Title	Duration of Response of Extracranial Disease
Description	Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Time Frame	Completion of treatment (estimated to be 6 months)

Outcome Measure Data

Analysis Population Description

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. The remaining two participants were not evaluable for this outcome measure because they didn't have an objective response per RECIST. There were not any participants enrolled in Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	0	0	0

10. Secondary Outcome

Title	Duration of Response Considering Both Intracranial and Extracranial Disease
Description	Defined as the interval from the first documentation of objective response (complete response or partial response) to the earlier of the first documentation of disease progression or death from any cause Intracranial disease: response and progression will be evaluated using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline Extracranial disease: response and progression will be evaluated using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Time Frame	Completion of treatment (estimated to be 6 months)

Outcome Measure Data

Analysis Population Description

Two participants were not evaluable in Cohort A as the extracranial response per RECIST was not done. The remaining two participants were not evaluable for this outcome measure because they didn't have an objective response. There were not any participants enrolled in Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	0	0	0

11. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Unequivocal progression of existing non-target lesions.
Time Frame	Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)

Outcome Measure Data

Analysis Population Description

There were not any participants enrolled in Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	4	0	0
Median (Full Range) [days]	51.5

12. Secondary Outcome

Title	Overall Survival (OS)
Description	-Defined as the interval from the start of study therapy to death from any cause
Time Frame	Up to 2 years after completion of treatment (estimated to be 2 years and 6 months)

Outcome Measure Data

Analysis Population Description

One participant in Cohort A was lost to follow-up and is not evaluable for this outcome measure. There were not any participants enrolled to Cohort B or Cohort C.

Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids	Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids	Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
Measure Participants	3	0	0
Median (Full Range) [days]	197

Adverse Events

Time Frame	Adverse events were collected starting at baseline and ending 30 days after the completion of treatment.
Adverse Event Reporting Description	There were no participants enrolled in Cohort B or C and that is why the number of participants at risk for All-Cause Mortality, Serious Adverse Events, and Other Adverse Events is zero.
Arm/Group Title	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids		Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids		Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
Arm/Group Description	-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.		-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.		-MEDI4736 will be given to all patients > 30 kg actual body weight intravenously at a fixed dose 750 mg every 2 weeks over the course of 60 minutes on an outpatient basis on Days 1 and 15 of each 28-day cycle. Patients < 30 kg actual body weight will be dosed at 10 mg/kg every 2 weeks.
All Cause Mortality
	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids		Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids		Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids		Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids		Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Nervous system disorders
Parasthesia	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Cohort A: Non-small Cell Lung Cancer w/o Corticosteroids		Cohort B: Epithelial Origin Solid Tumors w/o Corticosteroids		Cohort C: NSCLC or Non-NSCLC w/Corticosteroids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		0/0 (NaN)		0/0 (NaN)
Blood and lymphatic system disorders
Anemia	2/4 (50%)		0/0 (NaN)		0/0 (NaN)
Gastrointestinal disorders
Bloating	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Constipation	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Diarrhea	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Nausea	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
General disorders
Chills	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Fatigue	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Non-cardiac chest pain	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Night sweats	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Infections and infestations
Sinusitis	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Investigations
Lymphocyte count decreased	3/4 (75%)		0/0 (NaN)		0/0 (NaN)
Weight loss	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Metabolism and nutrition disorders
Hypercalcemia	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Hyperglycemia	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Hyponatremia	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Musculoskeletal and connective tissue disorders
Arthralgia	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Respiratory, thoracic and mediastinal disorders
Productive cough	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Post nasal drip	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Pruritus	1/4 (25%)		0/0 (NaN)		0/0 (NaN)
Vascular disorders
Hypertension	1/4 (25%)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.