SEASCAPE: Safety and Efficacy of CRS-207 With Epacadostat in Platinum Resistant Ovarian, Fallopian or Peritoneal Cancer

• Sponsor: Aduro Biotech, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02575807
• Collaborator: Incyte Corporation (Industry)
• Enrollment: 35
• Locations: 12
• Arms: 5
• Actual Duration (Months): 26
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This 2-part, Phase 1/2 study will test investigational cancer drugs known as CRS-207, epacadostat (IDO), and pembrolizumab (pembro). The purpose of this study is to find out how safe it is to give the investigational drugs to women with platinum-resistant ovarian, fallopian tube, or peritoneal cancer and if it helps patients with these types of cancer live longer or can help shrink or slow the growth of cancer.

Condition or Disease	Intervention/Treatment	Phase
Platinum-resistant Ovarian Cancer; Platinum-resistant Fallopian Cancer; Platinum-resistant Peritoneal Cancer	Biological: CRS-207; Drug: Epacadostat; Biological: Pembrolizumab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, Open-Label Safety and Efficacy Evaluation of CRS-207 in Combination With Epacadostat in Adults With Platinum-Resistant Ovarian, Fallopian, or Peritoneal Cancer
• Actual Study Start Date: Mar 8, 2016
• Actual Primary Completion Date: Apr 26, 2018
• Actual Study Completion Date: May 8, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1: CRS-207 CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 colony forming units [CFU]) administered by intravenous (IV) infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).	Biological: CRS-207; via IV infusion; Other Names: Live, attenuated double-deleted Listeria monocytogenes (LADD)
Experimental: Phase 1: CRS-207/IDO 100 mg CRS-207 administered in 3-week cycles, IDO administered twice daily (BID). CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (100 milligrams [mg]) administered by mouth (PO) BID, starting on Day 2 of the first CRS-207 treatment cycle.	Biological: CRS-207; via IV infusion; Other Names: Live, attenuated double-deleted Listeria monocytogenes (LADD) ; Drug: Epacadostat; PO BID; Other Names: INCB024360 IDO
Experimental: Phase 1: CRS-207/IDO 300 mg CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	Biological: CRS-207; via IV infusion; Other Names: Live, attenuated double-deleted Listeria monocytogenes (LADD) ; Drug: Epacadostat; PO BID; Other Names: INCB024360 IDO
Experimental: Phase 2: CRS-207/Pembro/IDO CRS-207 and pembrolizumab (pembro) administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles. IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.	Biological: CRS-207; via IV infusion; Other Names: Live, attenuated double-deleted Listeria monocytogenes (LADD) ; Drug: Epacadostat; PO BID; Other Names: INCB024360 IDO ; Biological: Pembrolizumab; via IV infusion; Other Names: Keytruda® Pembro
Experimental: Phase 2: CRS-207/Pembro CRS-207 and pembro administered in 3-week cycles. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.	Biological: CRS-207; via IV infusion; Other Names: Live, attenuated double-deleted Listeria monocytogenes (LADD) ; Biological: Pembrolizumab; via IV infusion; Other Names: Keytruda® Pembro

Outcome Measures

Primary Outcome Measures

1. Phase 1: Number of Subjects Reporting Hematologic and/or Non-hematologic Dose-limiting Toxicity (DLT) [Subjects followed for DLTs for 21 days following the first dose of CRS-207 (treatment Cycle 1 for CRS-207).]

   Count of subjects in the Phase 1 cohorts who reported a hematologic and/or non-hematologic DLT. Non-hematological DLTs are defined as follows, excluding the safety events specified for exemption in Section 5.3.1 of the study protocol: any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes that occurs during the DLT observation period (Cycle 1) and is Grade 3 or higher according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4; any use of systemic steroids; and/or a study drug dose interruption lasting ≥ 7 days for an adverse event with an unclear relationship to study drug. Hematological DLTs are defined as: Grade 4 neutropenia lasting >7 days; Grade ≥3 febrile neutropenia; Grade 4 anemia; Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia lasting >7 days or associated with bleeding; and/or Dose delay >7 days secondary to myelosuppression.

2. Phase 1: Adverse Events (AEs) by CTCAE Grade 3 or Higher [Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 3 months.]

   Count of subjects in the Phase 1 cohorts with incidences of CTCAE Grade 3 or higher AEs.

3. Phase 2: Adverse Events (AEs) [Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 2 months.]

   Count of subjects in the Phase 2 cohorts with incidences of AEs.

4. Phase 2: Objective Response Rate (ORR) [BOR was assessed from the first dose of study treatment until documented disease progression, initiation of a new cancer treatment, death, or study termination, whichever comes first, assessed up to 20 weeks.]

   ORR was evaluated for Phase 2 subjects based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each assessed subject as measured by modified response evaluation criteria in solid tumors (mRECIST) and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR mRECIST values of CR, PR, SD, PD, and NE are provided for this outcome measure.

5. Phase 2: Progression Free Survival (PFS) [Subjects followed for disease progression from first dose of study treatment until 30 days after last dose of study treatment or initiation of new cancer treatment, whichever comes first, assessed up to 20 weeks.]

   Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). PD is determined by mRECIST.

Secondary Outcome Measures

1. Phase 1: Objective Response Rate (ORR) by mRECIST [BOR was assessed from the first dose of study treatment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 100 weeks.]

   ORR was evaluated for Phase 1 subjects based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each assessed subject as measured by modified response evaluation criteria in solid tumors (mRECIST), RECIST v1.1, and GCIG CA-125 criteria and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR mRECIST values of CR, PR, SD, PD, and NE are provided for this outcome measure.

2. Phase 1: Progression Free Survival (PFS) [Subjects followed for disease progression from first dose of study treatment until 30 days after last dose of study treatment or initiation of new cancer treatment, whichever comes first, assessed up to 100 weeks]

   Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) or death due to any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). PD is determined by mRECIST, RECIST v1.1, and GCIG CA-125.

3. Disease Control Rate (DCR) [BOR was assessed from the first dose of study treatment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever comes first, assessed up to 100 weeks.]

   The protocol-specified DCR was defined as the percentage of evaluable subjects with a BOR of CR or PR, or SD as determined by mRECIST, RECIST v1.1, and GCIG CA-125 criteria.

4. Duration of Response (DOR) [Subjects followed for disease progression from date of CR or PR designation until documented disease progression or study termination, whichever comes first, assessed up to 100 weeks.]

   Number of weeks from date of CR or PR designation until PD designation, as determined by mRECIST, RECIST v1.1 and GCIG CA-125 criteria.

5. Overall Survival (OS) [OS was assessed from the first dose of study treatment until death or study termination, whichever comes first, assessed up to 100 weeks.]

   Number of weeks from the date of first dose of study treatment to the date of death from any cause, estimated using KM methods with 95% CIs for subjects in the SAF. Subjects without documentation of death at the time of analysis were censored as of the date the subject was last known to be alive. For subjects lost to follow up, the last visit or last contact date where the subject is documented to be alive will be used to estimate last known date alive.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Histologically-confirmed disease

• Phase 1: Individuals with epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinomas who are considered to have platinum-resistant disease (progression within 6 months from completion of platinum-based chemotherapy).

• Phase 2: Individuals with epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinomas who are considered to have platinum-resistant disease (progression within 6 months from completion of a minimum of 4 platinum therapy cycles).

1. Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

2. Agree to provide core biopsies at baseline and at Cycle 2 Day 15

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. Available archived tumor tissue for central analysis

5. Adequate organ and marrow function

Exclusion Criteria

1. Platinum-refractory disease (progression during the first platinum-based chemotherapy)

2. Major surgical procedure within 4 weeks prior to Study Day 1

3. Inaccessible tumors or for whom biopsy is contraindicated

4. Clinically significant ascites

5. Phase 2 only: Previous treatment with >3 chemotherapy regimens for locally advanced or metastatic disease

6. Active bowel obstruction, or hospitalization for bowel obstruction within 2 months prior to screening

7. Require parenteral nutrition

8. Hospitalization within 2 weeks prior to screening

9. Received any anticancer medication or therapy in the 21 days prior to study Day 1

10. Prior monoclonal antibody treatment within 4 weeks before study Day 1

11. History of listeriosis or previous treatment with a listeria-based immunotherapy

12. Known allergy to both penicillin and sulfa antibiotics

13. Any immunodeficiency disease or immune-compromised state

14. Received prior immune checkpoint inhibitors (e.g., anti-CTLA-4, anti-PD-1, anti PDL-1) and any other antibody or drug specifically targeting T-cell costimulation or an IDO inhibitor

15. Pregnant or breastfeeding

16. Clinically significant heart disease

17. Valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis

18. History of any autoimmune disease which required systemic therapy in the past 2 years

19. Diagnosed with another malignancy within the past 3 years

20. Currently receiving therapy with a UDP-glucuronosyltransferase 1A9 inhibitor including diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid

21. Receiving monoamine oxidase inhibitor (MAOIs) or a drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening

22. Had prior serotonin syndrome

23. Has implanted medical devices that pose high risks for colonization and cannot be easily removed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Scottsdale Healthcare Hospitals DBA HonorHealth	Scottsdale	Arizona	United States	85258
2	Stanford Cancer Center	Stanford	California	United States	94305
3	University of Florida	Gainesville	Florida	United States	32610
4	Northwestern University	Chicago	Illinois	United States	60611
5	Johns Hopkins University	Baltimore	Maryland	United States	21287
6	Oregon Health and Science University	Portland	Oregon	United States	97239
7	University of Pennsylvania Health System	Philadelphia	Pennsylvania	United States	19104
8	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
9	University of Virginia Health System	Charlottesville	Virginia	United States	22903
10	Virginia Mason Medical Center	Seattle	Washington	United States	98101
11	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
12	CHUM - Centre Hospitalier de l'Université de Montréal	Montréal	Quebec	Canada	H2X 0A9

Sponsors and Collaborators

• Aduro Biotech, Inc.
• Incyte Corporation

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Feb 18, 2017
• Statistical Analysis Plan - May 3, 2018

More Information

Publications

None provided.

• Responsible Party: Aduro Biotech, Inc.
• ClinicalTrials.gov Identifier: NCT02575807
• Other Study ID Numbers: ADU-CL-11
• First Posted: Oct 15, 2015
• Last Update Posted: Apr 4, 2019
• Last Verified: Apr 1, 2019

• 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
• Keywords provided by Aduro Biotech, Inc.: Ovarian cancer; Fallopian cancer; Primary peritoneal cancer
• Additional relevant MeSH terms: Ovarian Neoplasms; Peritoneal Neoplasms; Pembrolizumab

Study Results

Participant Flow

Arm/Group Title	Phase 1: CRS-207	Phase 1: CRS-207/IDO 100 mg	Phase 1: CRS-207/IDO 300 mg	Phase 2: CRS-207/Pembro/IDO	Phase 2: CRS-207/Pembro
Arm/Group Description	CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 colony forming units [CFU]) administered by intravenous (IV) infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).	CRS-207 administered in 3-week cycles, epacadostat (IDO) administered twice daily (BID). CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (100 milligrams [mg]) administered by mouth (PO) BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 and pembrolizumab (pembro) administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles. IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.
Period Title: Overall Study
STARTED	9	4	16	2	4
Treated	8	4	16	1	3
COMPLETED	0	0	0	0	0
NOT COMPLETED	9	4	16	2	4

Baseline Characteristics

Arm/Group Title	Phase 1: CRS-207	Phase 1: CRS-207/IDO 100 mg	Phase 1: CRS-207/IDO 300 mg	Phase 2: CRS-207/Pembro/IDO	Phase 2: CRS-207/Pembro	Total
Arm/Group Description	CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles. IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.	Total of all reporting groups
Overall Participants	8	4	16	1	3	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.1 (11.03)	62.0 (12.99)	62.4 (9.35)	60.0 (NA)	61.7 (5.13)	61.9 (9.39)
Sex: Female, Male (Count of Participants)
Female	8 100%	4 100%	16 100%	1 100%	3 100%	32 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 12.5%	0 0%	1 6.3%	0 0%	0 0%	2 6.3%
Not Hispanic or Latino	7 87.5%	4 100%	15 93.8%	1 100%	3 100%	30 93.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	1 33.3%	1 3.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	8 100%	3 75%	15 93.8%	1 100%	2 66.7%	29 90.6%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 25%	1 6.3%	0 0%	0 0%	2 6.3%
Region of Enrollment (Count of Participants)
Canada	0 0%	0 0%	2 12.5%	0 0%	0 0%	2 6.3%
United States	8 100%	4 100%	14 87.5%	1 100%	3 100%	30 93.8%

Outcome Measures

1. Primary Outcome

Title	Phase 1: Number of Subjects Reporting Hematologic and/or Non-hematologic Dose-limiting Toxicity (DLT)
Description	Count of subjects in the Phase 1 cohorts who reported a hematologic and/or non-hematologic DLT. Non-hematological DLTs are defined as follows, excluding the safety events specified for exemption in Section 5.3.1 of the study protocol: any treatment-emergent adverse event (TEAE) not attributable to disease or disease-related processes that occurs during the DLT observation period (Cycle 1) and is Grade 3 or higher according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4; any use of systemic steroids; and/or a study drug dose interruption lasting ≥ 7 days for an adverse event with an unclear relationship to study drug. Hematological DLTs are defined as: Grade 4 neutropenia lasting >7 days; Grade ≥3 febrile neutropenia; Grade 4 anemia; Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia lasting >7 days or associated with bleeding; and/or Dose delay >7 days secondary to myelosuppression.
Time Frame	Subjects followed for DLTs for 21 days following the first dose of CRS-207 (treatment Cycle 1 for CRS-207).

Outcome Measure Data

Analysis Population Description

Analysis performed on subjects in the Phase 1 safety analysis set (SAF).

Arm/Group Title	Phase 1: CRS-207	Phase 1: CRS-207/IDO 100 mg	Phase 1: CRS-207/IDO 300 mg
Arm/Group Description	CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.
Measure Participants	8	4	16
Count of Participants [Participants]	1 12.5%	0 0%	1 6.3%

2. Primary Outcome

Title	Phase 1: Adverse Events (AEs) by CTCAE Grade 3 or Higher
Description	Count of subjects in the Phase 1 cohorts with incidences of CTCAE Grade 3 or higher AEs.
Time Frame	Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 3 months.

Outcome Measure Data

Analysis Population Description

Analysis performed on subjects in the Phase 1 safety analysis set.

Arm/Group Title	Phase 1: CRS-207	Phase 1: CRS-207/IDO 100 mg	Phase 1: CRS-207/IDO 300 mg
Arm/Group Description	CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.
Measure Participants	8	4	16
Count of Participants [Participants]	6 75%	3 75%	14 87.5%

3. Primary Outcome

Title	Phase 2: Adverse Events (AEs)
Description	Count of subjects in the Phase 2 cohorts with incidences of AEs.
Time Frame	Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 2 months.

Outcome Measure Data

Analysis Population Description

Analysis performed on subjects in the Phase 2 safety analysis set.

Arm/Group Title	Phase 2: CRS-207/Pembro/IDO	Phase 2: CRS-207/Pembro
Arm/Group Description	CRS-207 and pembro administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles. IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.
Measure Participants	1	3
Count of Participants [Participants]	1 12.5%	3 75%

4. Primary Outcome

Title	Phase 2: Objective Response Rate (ORR)
Description	ORR was evaluated for Phase 2 subjects based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each assessed subject as measured by modified response evaluation criteria in solid tumors (mRECIST) and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR mRECIST values of CR, PR, SD, PD, and NE are provided for this outcome measure.
Time Frame	BOR was assessed from the first dose of study treatment until documented disease progression, initiation of a new cancer treatment, death, or study termination, whichever comes first, assessed up to 20 weeks.

Outcome Measure Data

Analysis Population Description

Analysis performed on subjects in the SAF who had ≥1 post-baseline response assessment. One subject in the Phase 2 SAF did not complete ≥1 post-baseline response assessment and was therefore not evaluated for this outcome measure.

Arm/Group Title	Phase 2: CRS-207/Pembro/IDO	Phase 2: CRS-207/Pembro
Arm/Group Description	CRS-207 and pembro administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles. IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.
Measure Participants	1	2
Complete Response	0 0%	0 0%
Partial Response	0 0%	0 0%
Stable Disease	0 0%	0 0%
Progressive Disease	1 12.5%	2 50%
Not Evaluable	0 0%	0 0%

5. Secondary Outcome

Title	Phase 1: Objective Response Rate (ORR) by mRECIST
Description	ORR was evaluated for Phase 1 subjects based upon the best overall response (BOR) for individual study subjects. BOR was determined by the highest post-baseline qualitative response value for each assessed subject as measured by modified response evaluation criteria in solid tumors (mRECIST), RECIST v1.1, and GCIG CA-125 criteria and given the following hierarchy of overall response results: complete response (CR) > partial response (PR) > stable disease (SD) > progressive disease (PD) > not evaluable (NE). The protocol-specified ORR was defined as the percentage of evaluable subjects with a BOR of CR or PR; however, this percentage was not calculated per the final study Statistical Analysis Plan (SAP). Therefore, the number of evaluable subjects with BOR mRECIST values of CR, PR, SD, PD, and NE are provided for this outcome measure.
Time Frame	BOR was assessed from the first dose of study treatment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever is earlier, assessed up to 100 weeks.

Outcome Measure Data

Analysis Population Description

Analysis performed on subjects in the SAF who had ≥1 post-baseline response assessment. Three subjects in the Phase 1 SAF did not complete ≥1 post-baseline response assessment and were therefore not evaluated for this outcome measure.

Arm/Group Title	Phase 1: CRS-207	Phase 1: CRS-207/IDO 100 mg	Phase 1: CRS-207/IDO 300 mg
Arm/Group Description	CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.
Measure Participants	8	4	13
Complete Response	0 0%	0 0%	0 0%
Partial Response	0 0%	0 0%	0 0%
Stable Disease	1 12.5%	1 25%	4 25%
Progressive Disease	7 87.5%	3 75%	6 37.5%
Not Evaluable	0 0%	0 0%	3 18.8%

6. Secondary Outcome

Title	Phase 1: Progression Free Survival (PFS)
Description	Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) or death due to any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). PD is determined by mRECIST, RECIST v1.1, and GCIG CA-125.
Time Frame	Subjects followed for disease progression from first dose of study treatment until 30 days after last dose of study treatment or initiation of new cancer treatment, whichever comes first, assessed up to 100 weeks

Outcome Measure Data

Analysis Population Description

Analysis performed on subjects in the Phase 1 SAF.

Arm/Group Title	Phase 1: CRS-207	Phase 1: CRS-207/IDO 100 mg	Phase 1: CRS-207/IDO 300 mg
Arm/Group Description	CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.
Measure Participants	8	4	16
Median (95% Confidence Interval) [weeks]	8.43	4.71	8.43

7. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	The protocol-specified DCR was defined as the percentage of evaluable subjects with a BOR of CR or PR, or SD as determined by mRECIST, RECIST v1.1, and GCIG CA-125 criteria.
Time Frame	BOR was assessed from the first dose of study treatment until documented disease progression, starting of a new cancer treatment, death, or study termination, whichever comes first, assessed up to 100 weeks.

Outcome Measure Data

Analysis Population Description

Analysis performed on subjects in the Phase 1 and Phase 2 SAF.

Arm/Group Title	Phase 1: CRS-207	Phase 1: CRS-207/IDO 100 mg	Phase 1: CRS-207/IDO 300 mg	Phase 2: CRS-207/Pembro/IDO	Phase 2: CRS-207/Pembro
Arm/Group Description	CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles. IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.
Measure Participants	8	4	16	1	3
Complete Response (CR)	0 0%	0 0%	0 0%	0 0%	0 0%
Partial Response (PR)	0 0%	0 0%	0 0%	0 0%	0 0%
Stable Disease (SD)	1 12.5%	1 25%	4 25%	0 0%	0 0%

8. Secondary Outcome

Title	Duration of Response (DOR)
Description	Number of weeks from date of CR or PR designation until PD designation, as determined by mRECIST, RECIST v1.1 and GCIG CA-125 criteria.
Time Frame	Subjects followed for disease progression from date of CR or PR designation until documented disease progression or study termination, whichever comes first, assessed up to 100 weeks.

Outcome Measure Data

Analysis Population Description

No study subjects achieved CR or PR designation; therefore, per the final SAP DOR was not derived.

Arm/Group Title	Phase 1: CRS-207	Phase 1: CRS-207/IDO 100 mg	Phase 1: CRS-207/IDO 300 mg	Phase 2: CRS-207/Pembro/IDO	Phase 2: CRS-207/Pembro
Arm/Group Description	CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles. IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.
Measure Participants	8	4	16	1	3
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

9. Secondary Outcome

Title	Overall Survival (OS)
Description	Number of weeks from the date of first dose of study treatment to the date of death from any cause, estimated using KM methods with 95% CIs for subjects in the SAF. Subjects without documentation of death at the time of analysis were censored as of the date the subject was last known to be alive. For subjects lost to follow up, the last visit or last contact date where the subject is documented to be alive will be used to estimate last known date alive.
Time Frame	OS was assessed from the first dose of study treatment until death or study termination, whichever comes first, assessed up to 100 weeks.

Outcome Measure Data

Analysis Population Description

Analysis performed on subjects in the Phase 1 and Phase 2 SAF.

Arm/Group Title	Phase 1: CRS-207	Phase 1: CRS-207/IDO 100 mg	Phase 1: CRS-207/IDO 300 mg	Phase 2: CRS-207/Pembro/IDO	Phase 2: CRS-207/Pembro
Arm/Group Description	CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles. IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.
Measure Participants	8	4	16	1	3
Median (95% Confidence Interval) [weeks]	49.07	30.00	27.00	9.29	18.43

10. Primary Outcome

Title	Phase 2: Progression Free Survival (PFS)
Description	Number of weeks from the date of first dose of study treatment to the first date of objectively determined progressive disease (PD) or death from any cause, estimated using Kaplan-Meier (KM) methods with 95% confidence intervals (CIs). PD is determined by mRECIST.
Time Frame	Subjects followed for disease progression from first dose of study treatment until 30 days after last dose of study treatment or initiation of new cancer treatment, whichever comes first, assessed up to 20 weeks.

Outcome Measure Data

Analysis Population Description

Analysis performed on subjects in the Phase 2 SAF.

Arm/Group Title	Phase 2: CRS-207/Pembro/IDO	Phase 2: CRS-207/Pembro
Arm/Group Description	CRS-207 and pembro administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles. IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.	CRS-207 and pembro administered in 3-week cycles. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.
Measure Participants	1	3
Median (95% Confidence Interval) [weeks]	5.71	7.36

Adverse Events

Time Frame	Subjects were followed for serious and non-serious adverse events (AEs) from the beginning of any study drug until 30 days following the last dose of study drug, an average of 3 months. Subjects were followed for survival until withdrawal of consent, loss to follow-up, death, or study termination (whichever is first), an average of 35 weeks.
Adverse Event Reporting Description	AEs reported for the Safety Analysis Set (SAF). Methods of determining whether certain AEs have occurred include regular investigator assessment and regular laboratory testing.
Arm/Group Title	Phase 1: CRS-207		Phase 1: CRS-207/IDO 100 mg		Phase 1: CRS-207/IDO 300 mg		Phase 2: CRS-207/Pembro/IDO		Phase 2: CRS-207/Pembro
Arm/Group Description	CRS-207 administered in 3-week cycles. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 will be administered on Day 1 of each cycle. After 6 cycles, CRS-207 will be administered on Day 1 once every 6 weeks (every other cycle).		CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.		CRS-207 administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 1 of each cycle. After 6 cycles, CRS-207 administered on Day 1 once every 6 weeks (every other cycle). IDO (300 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.		CRS-207 and pembro administered in 3-week cycles, IDO administered BID. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles. IDO (300 mg) administered PO BID, starting on Day 3 of the first CRS-207 treatment cycle.		CRS-207 and pembro administered in 3-week cycles. CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.
All Cause Mortality
	Phase 1: CRS-207		Phase 1: CRS-207/IDO 100 mg		Phase 1: CRS-207/IDO 300 mg		Phase 2: CRS-207/Pembro/IDO		Phase 2: CRS-207/Pembro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		3/4 (75%)		7/16 (43.8%)		1/1 (100%)		1/3 (33.3%)
Serious Adverse Events
	Phase 1: CRS-207		Phase 1: CRS-207/IDO 100 mg		Phase 1: CRS-207/IDO 300 mg		Phase 2: CRS-207/Pembro/IDO		Phase 2: CRS-207/Pembro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		1/4 (25%)		9/16 (56.3%)		1/1 (100%)		1/3 (33.3%)
Gastrointestinal disorders
Abdominal pain	0/8 (0%)		0/4 (0%)		3/16 (18.8%)		0/1 (0%)		0/3 (0%)
Small intestinal obstruction	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		1/1 (100%)		0/3 (0%)
Ascites	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Enterovesical fistula	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Intestinal perforation	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Pancreatitis	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Constipation	0/8 (0%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		1/3 (33.3%)
Large intestine perforation	0/8 (0%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		1/3 (33.3%)
General disorders
Disease progression	0/8 (0%)		0/4 (0%)		0/16 (0%)		1/1 (100%)		0/3 (0%)
Infections and infestations
Bacteraemia	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Sepsis	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Injury, poisoning and procedural complications
Infusion related reaction	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Investigations
Amylase increased	0/8 (0%)		1/4 (25%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/8 (0%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		1/3 (33.3%)
Nervous system disorders
Seizure	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Syncope	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Renal and urinary disorders
Hydronephrosis	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Phase 1: CRS-207		Phase 1: CRS-207/IDO 100 mg		Phase 1: CRS-207/IDO 300 mg		Phase 2: CRS-207/Pembro/IDO		Phase 2: CRS-207/Pembro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		4/4 (100%)		16/16 (100%)		1/1 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Leukocytosis	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Lymphadenopathy	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Cardiac disorders
Tachycardia	2/8 (25%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Bradycardia	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Ear and labyrinth disorders
Ear discomfort	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Tinnitus	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Eye disorders
Vision blurred	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Visual acuity reduced	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Gastrointestinal disorders
Nausea	6/8 (75%)		1/4 (25%)		10/16 (62.5%)		0/1 (0%)		1/3 (33.3%)
Vomiting	6/8 (75%)		1/4 (25%)		9/16 (56.3%)		0/1 (0%)		0/3 (0%)
Abdominal pain	4/8 (50%)		1/4 (25%)		8/16 (50%)		0/1 (0%)		0/3 (0%)
Constipation	1/8 (12.5%)		0/4 (0%)		6/16 (37.5%)		0/1 (0%)		1/3 (33.3%)
Diarrhoea	2/8 (25%)		1/4 (25%)		4/16 (25%)		0/1 (0%)		0/3 (0%)
Abdominal distension	1/8 (12.5%)		1/4 (25%)		4/16 (25%)		0/1 (0%)		0/3 (0%)
Ascites	1/8 (12.5%)		1/4 (25%)		4/16 (25%)		0/1 (0%)		0/3 (0%)
Abdominal pain upper	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		1/1 (100%)		0/3 (0%)
Dry mouth	1/8 (12.5%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Enterovesical fistula	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Small intestinal obstruction	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		1/1 (100%)		0/3 (0%)
Abdominal tenderness	0/8 (0%)		1/4 (25%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Aphthous ulcer	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Flatulence	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Gastrooesophageal reflux disease	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Gingival bleeding	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Intestinal perforation	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Lip blister	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Mucous stools	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Pancreatitis	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Dysphagia	0/8 (0%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		1/3 (33.3%)
Large intestine perforation	0/8 (0%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		1/3 (33.3%)
General disorders
Chills	7/8 (87.5%)		4/4 (100%)		12/16 (75%)		1/1 (100%)		3/3 (100%)
Pyrexia	7/8 (87.5%)		2/4 (50%)		14/16 (87.5%)		0/1 (0%)		2/3 (66.7%)
Fatigue	3/8 (37.5%)		2/4 (50%)		11/16 (68.8%)		0/1 (0%)		1/3 (33.3%)
Influenza like illness	1/8 (12.5%)		0/4 (0%)		3/16 (18.8%)		0/1 (0%)		1/3 (33.3%)
Early satiety	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Malaise	1/8 (12.5%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Oedema	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Pain	1/8 (12.5%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		1/3 (33.3%)
Asthenia	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Catheter site pain	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Hunger	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Injection site erythema	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Oedema peripheral	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Disease progression	0/8 (0%)		0/4 (0%)		0/16 (0%)		1/1 (100%)		0/3 (0%)
Immune system disorders
Hypersensitivity	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		1/1 (100%)		0/3 (0%)
Infections and infestations
Bacteraemia	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Listeriosis	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Oral herpes	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Sepsis	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Upper respiratory tract infection	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Urinary tract infection	0/8 (0%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		1/3 (33.3%)
Injury, poisoning and procedural complications
Infusion related reaction	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Procedural pain	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Investigations
Lymphocyte count decreased	1/8 (12.5%)		2/4 (50%)		5/16 (31.3%)		0/1 (0%)		0/3 (0%)
Aspartate aminotransferase increased	1/8 (12.5%)		0/4 (0%)		5/16 (31.3%)		0/1 (0%)		0/3 (0%)
Alanine aminotransferase increased	1/8 (12.5%)		0/4 (0%)		4/16 (25%)		0/1 (0%)		0/3 (0%)
Blood creatinine increased	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Amylase increased	0/8 (0%)		1/4 (25%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Blood bilirubin increased	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Blood magnesium decreased	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Blood urea increased	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Glomerular filtration rate decreased	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Lipase increased	0/8 (0%)		1/4 (25%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Neutrophil count decreased	0/8 (0%)		1/4 (25%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Neutrophil count increased	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Weight decreased	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
White blood cell count decreased	0/8 (0%)		1/4 (25%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Metabolism and nutrition disorders
Decreased appetite	3/8 (37.5%)		0/4 (0%)		6/16 (37.5%)		0/1 (0%)		1/3 (33.3%)
Hypokalaemia	1/8 (12.5%)		0/4 (0%)		4/16 (25%)		0/1 (0%)		0/3 (0%)
Hypomagnesaemia	1/8 (12.5%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Hyponatraemia	0/8 (0%)		0/4 (0%)		3/16 (18.8%)		0/1 (0%)		0/3 (0%)
Dehydration	1/8 (12.5%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Hypophosphataemia	1/8 (12.5%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Malnutrition	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Hyperglycaemia	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		1/1 (100%)		0/3 (0%)
Hypoalbuminaemia	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Iron deficiency	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Polydipsia	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Back pain	6/8 (75%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Myalgia	2/8 (25%)		0/4 (0%)		3/16 (18.8%)		0/1 (0%)		0/3 (0%)
Arthralgia	1/8 (12.5%)		0/4 (0%)		3/16 (18.8%)		0/1 (0%)		1/3 (33.3%)
Muscle spasms	0/8 (0%)		0/4 (0%)		4/16 (25%)		0/1 (0%)		0/3 (0%)
Muscle tightness	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Musculoskeletal pain	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		1/3 (33.3%)
Neck pain	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Flank pain	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Groin pain	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Joint stiffness	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Muscle twitching	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Pain in extremity	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Bone pain	0/8 (0%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		1/3 (33.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		1/3 (33.3%)
Nervous system disorders
Headache	4/8 (50%)		2/4 (50%)		10/16 (62.5%)		0/1 (0%)		2/3 (66.7%)
Dizziness	2/8 (25%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Syncope	1/8 (12.5%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Dysgeusia	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Myoclonus	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Neuropathy peripheral	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Presyncope	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Seizure	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Psychiatric disorders
Confusional state	1/8 (12.5%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Insomnia	2/8 (25%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Anxiety	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Bruxism	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Hallucination	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Renal and urinary disorders
Acute kidney injury	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Dysuria	1/8 (12.5%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		1/3 (33.3%)
Hydronephrosis	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Haematuria	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Incontinence	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Micturition urgency	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Pollakiuria	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Urinary incontinence	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/8 (12.5%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Oedema genital	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	3/8 (37.5%)		0/4 (0%)		5/16 (31.3%)		0/1 (0%)		0/3 (0%)
Dyspnoea	2/8 (25%)		0/4 (0%)		5/16 (31.3%)		0/1 (0%)		0/3 (0%)
Cough	0/8 (0%)		2/4 (50%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Pleural effusion	1/8 (12.5%)		1/4 (25%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Nasal congestion	1/8 (12.5%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Rhinorrhoea	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Chronic obstructive pulmonary disease	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Dyspnoea exertional	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Oropharyngeal pain	0/8 (0%)		1/4 (25%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Paranasal sinus hypersecretion	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Productive cough	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Upper-airway cough syndrome	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Hiccups	0/8 (0%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		1/3 (33.3%)
Skin and subcutaneous tissue disorders
Rash	0/8 (0%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Dry skin	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Pain of skin	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Pruritus	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Rash maculo-papular	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Rash pruritic	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)
Skin irritation	1/8 (12.5%)		0/4 (0%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Urticaria	0/8 (0%)		1/4 (25%)		0/16 (0%)		0/1 (0%)		0/3 (0%)
Vascular disorders
Hypotension	3/8 (37.5%)		2/4 (50%)		3/16 (18.8%)		0/1 (0%)		0/3 (0%)
Hypertension	1/8 (12.5%)		0/4 (0%)		2/16 (12.5%)		0/1 (0%)		0/3 (0%)
Hot flush	0/8 (0%)		0/4 (0%)		1/16 (6.3%)		0/1 (0%)		0/3 (0%)

Limitations/Caveats

Study was terminated early and included a small number of subjects, and insufficient data were available to evaluate the clinical activity of the study treatment. Due to low enrollment, some protocol-specified outcome measures were not evaluated.

More Information

Certain Agreements

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

The only disclosure restriction is that study results will first be published in a joint multi-center paper unless (a) written confirmation is provided to the site or PI indicating that there will be no multi-center publication, or (b) at least 12 months have passed after the completion of data analysis at all study sites. Publications will be submitted for sponsor review ≥ 45 days prior to the publication date. Sponsor cannot require changes to the communication or extend the embargo.