Safety and Efficacy of CRS-207 With Epacadostat in Platin... | NCT02575807

NCT02575807

Status Module

Sponsor/Collaborators Module

Name	Class
Incyte Corporation	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Phase 1: CRS-207	Experimental	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
Phase 1: CRS-207/IDO 100 mg	Experimental	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 Drug: Epacadostat
Phase 1: CRS-207/IDO 300 mg	Experimental	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 Drug: Epacadostat
Phase 2: CRS-207/Pembro/IDO	Experimental	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.

Name	Type	Description	Arm Group Labels	Other Names
CRS-207	Biological	via IV infusion	Phase 1: CRS-207 Phase 1: CRS-207/IDO 100 mg Phase 1: CRS-207/IDO 300 mg Phase 2: CRS-207/Pembro

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase 1: Number of Subjects Reporting Hematologic and/or Non-hematologic Dose-limiting Toxicity (DLT)	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.	Subjects followed for DLTs for 21 days following the first dose of CRS-207 (treatment Cycle 1 for CRS-207).
Phase 1: Adverse Events (AEs) by CTCAE Grade 3 or Higher	Count of subjects in the Phase 1 cohorts with incidences of CTCAE Grade 3 or higher AEs.	Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 3 months.
Phase 2: Adverse Events (AEs)	Count of subjects in the Phase 2 cohorts with incidences of AEs.	Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 2 months.
Phase 2: Objective Response Rate (ORR)	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.

Secondary Outcomes

Measure	Description	Time Frame
Phase 1: Objective Response Rate (ORR) by mRECIST	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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).
Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Agree to provide core biopsies at baseline and at Cycle 2 Day 15
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Available archived tumor tissue for central analysis
Adequate organ and marrow function

Exclusion Criteria

Platinum-refractory disease (progression during the first platinum-based chemotherapy)
Major surgical procedure within 4 weeks prior to Study Day 1
Inaccessible tumors or for whom biopsy is contraindicated
Clinically significant ascites
Phase 2 only: Previous treatment with >3 chemotherapy regimens for locally advanced or metastatic disease
Active bowel obstruction, or hospitalization for bowel obstruction within 2 months prior to screening
Require parenteral nutrition
Hospitalization within 2 weeks prior to screening
Received any anticancer medication or therapy in the 21 days prior to study Day 1
Prior monoclonal antibody treatment within 4 weeks before study Day 1
History of listeriosis or previous treatment with a listeria-based immunotherapy
Known allergy to both penicillin and sulfa antibiotics
Any immunodeficiency disease or immune-compromised state
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
Pregnant or breastfeeding
Clinically significant heart disease
Valvular heart disease that requires antibiotic prophylaxis for prevention of endocarditis
History of any autoimmune disease which required systemic therapy in the past 2 years
Diagnosed with another malignancy within the past 3 years
Currently receiving therapy with a UDP-glucuronosyltransferase 1A9 inhibitor including diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid
Receiving monoamine oxidase inhibitor (MAOIs) or a drug which has significant MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before screening
Had prior serotonin syndrome
Has implanted medical devices that pose high risks for colonization and cannot be easily removed

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Scottsdale Healthcare Hospitals DBA HonorHealth		Scottsdale	Arizona	85258	United States
Stanford Cancer Center

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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).
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 18, 2017	Dec 14, 2018

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Phase 2: CRS-207/Pembro/IDO

Baseline analysis provided for all subjects who were administered at least 1 dose of protocol-specified drug (the Safety Analysis Set [SAF]).

Arm/Group Information

ID	Title	Description
BG000	Phase 1: CRS-207	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).
BG001	Phase 1: CRS-207/IDO 100 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 (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.
BG002	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.
BG003	Phase 2: CRS-207/Pembro/IDO	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.
BG004	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.
BG005	Total	Total of all reporting groups

Units	Counts
Participants	BG0008 BG0014 BG00216 BG0031 BG0043 BG00532

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00061.1± 11.03 BG00162.0± 12.99 BG00262.4± 9.35 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0008 BG0014 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

Canada

Title	Measurements
	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase 1: Number of Subjects Reporting Hematologic and/or Non-hematologic Dose-limiting Toxicity (DLT)

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.

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

Posted

Count of Participants

Participants

Subjects followed for DLTs for 21 days following the first dose of CRS-207 (treatment Cycle 1 for CRS-207).

ID	Title	Description
OG000	Phase 1: CRS-207	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).
OG001	Phase 1: CRS-207/IDO 100 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 (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.
OG002	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.

Units	Counts
Participants	OG0008 OG0014 OG00216

Title

Denominators

Categories

Title	Measurements
	OG0001 OG0010 OG0021

Primary

Phase 1: Adverse Events (AEs) by CTCAE Grade 3 or Higher

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

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

Posted

Count of Participants

Participants

Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 3 months.

ID	Title	Description
OG000	Phase 1: CRS-207	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).
OG001	Phase 1: CRS-207/IDO 100 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 (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.
OG002	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.

Primary

Phase 2: Adverse Events (AEs)

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

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

Posted

Count of Participants

Participants

Subjects followed from the start of study treatment until 30 days following the final dose of study drug, an average of 2 months.

ID	Title	Description
OG000	Phase 2: CRS-207/Pembro/IDO	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.
OG001	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.

Primary

Phase 2: Objective Response Rate (ORR)

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.

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.

Posted

Count of Participants

Participants

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.

ID	Title	Description
OG000	Phase 2: CRS-207/Pembro/IDO	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.

Secondary

Phase 1: Objective Response Rate (ORR) by mRECIST

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.

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.

Posted

Count of Participants

Participants

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.

ID	Title	Description
OG000	Phase 1: CRS-207	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).

Secondary

Phase 1: Progression Free Survival (PFS)

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.

Analysis performed on subjects in the Phase 1 SAF.

Posted

Median

95% Confidence Interval

weeks

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

ID	Title	Description
OG000	Phase 1: CRS-207	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).
OG001	Phase 1: CRS-207/IDO 100 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 (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.

Secondary

Disease Control Rate (DCR)

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.

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

Posted

Count of Participants

Participants

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.

ID	Title	Description
OG000	Phase 1: CRS-207	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).
OG001	Phase 1: CRS-207/IDO 100 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 (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.
OG002	Phase 1: CRS-207/IDO 300 mg

Secondary

Duration of Response (DOR)

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.

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

Posted

Count of Participants

Participants

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.

ID	Title	Description
OG000	Phase 1: CRS-207	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).
OG001	Phase 1: CRS-207/IDO 100 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 (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.
OG002	Phase 1: CRS-207/IDO 300 mg

Secondary

Overall Survival (OS)

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.

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

Posted

Median

95% Confidence Interval

weeks

OS was assessed from the first dose of study treatment until death or study termination, whichever comes first, assessed up to 100 weeks.

ID	Title	Description
OG000	Phase 1: CRS-207	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).
OG001	Phase 1: CRS-207/IDO 100 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 (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.

Primary

Phase 2: Progression Free Survival (PFS)

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.

Analysis performed on subjects in the Phase 2 SAF.

Posted

Median

95% Confidence Interval

weeks

ID	Title	Description
OG000	Phase 2: CRS-207/Pembro/IDO	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.
OG001	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1: CRS-207	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).	8	8	2	8	8	8
EG001	Phase 1: CRS-207/IDO 100 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 (100 mg) administered PO BID, starting on Day 2 of the first CRS-207 treatment cycle.	3	4	1	4	4	4
EG002	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.	7	16	9	16	16	16
EG003	Phase 2: CRS-207/Pembro/IDO	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.	1	1	1	1	1	1
EG004	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.	1	3	1	3	3	3

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0023 affected16 at risk EG0030 affected1 at risk EG0040 affected3 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Enterovesical fistula	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Intestinal perforation	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Large intestine perforation	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Bacteraemia	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Sepsis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Seizure	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Syncope	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Amylase increased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0011 affected4 at risk EG0020 affected16 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Disease progression	General disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0006 affected8 at risk EG0011 affected4 at risk EG00210 affected16 at risk EG0030 affected1 at risk EG0041 affected3 at risk
Vomiting	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0006 affected8 at risk EG0011 affected4 at risk EG0029 affected16 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0004 affected8 at risk EG0011 affected4 at risk EG0028 affected16 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0026 affected16 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected8 at risk EG0011 affected4 at risk EG0024 affected16 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0011 affected4 at risk EG0024 affected16 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0011 affected4 at risk EG0024 affected16 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Enterovesical fistula	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Abdominal tenderness	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0011 affected4 at risk EG0020 affected16 at risk EG003
Aphthous ulcer	Gastrointestinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Intestinal perforation	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Lip blister	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Mucous stools	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Large intestine perforation	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Chills	General disorders	MedDRA (19.0)	Systematic Assessment	EG0007 affected8 at risk EG0014 affected4 at risk EG00212 affected16 at risk EG003
Pyrexia	General disorders	MedDRA (19.0)	Systematic Assessment	EG0007 affected8 at risk EG0012 affected4 at risk EG00214 affected16 at risk EG003
Fatigue	General disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected8 at risk EG0012 affected4 at risk EG00211 affected16 at risk EG003
Influenza like illness	General disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0023 affected16 at risk EG003
Early satiety	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Malaise	General disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Oedema	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Pain	General disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Asthenia	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Catheter site pain	General disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Hunger	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Injection site erythema	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Oedema peripheral	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Disease progression	General disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Headache	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0004 affected8 at risk EG0012 affected4 at risk EG00210 affected16 at risk EG003
Dizziness	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Syncope	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Myoclonus	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Presyncope	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Seizure	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 affected8 at risk EG0010 affected4 at risk EG0025 affected16 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected8 at risk EG0010 affected4 at risk EG0025 affected16 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0012 affected4 at risk EG0021 affected16 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0011 affected4 at risk EG0021 affected16 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0011 affected4 at risk EG0020 affected16 at risk EG003
Paranasal sinus hypersecretion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 affected8 at risk EG0010 affected4 at risk EG0026 affected16 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0024 affected16 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0023 affected16 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Malnutrition	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Iron deficiency	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Polydipsia	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0006 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected8 at risk EG0010 affected4 at risk EG0023 affected16 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0023 affected16 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0024 affected16 at risk EG003
Muscle tightness	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Joint stiffness	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Muscle twitching	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA (19.0)	Non-systematic Assessment	EG0001 affected8 at risk EG0012 affected4 at risk EG0025 affected16 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0025 affected16 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0024 affected16 at risk EG003
Blood creatinine increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Amylase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0011 affected4 at risk EG0020 affected16 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Blood magnesium decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Blood urea increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Glomerular filtration rate decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Lipase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0011 affected4 at risk EG0020 affected16 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0011 affected4 at risk EG0020 affected16 at risk EG003
Neutrophil count increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Weight decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
White blood cell count decreased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0011 affected4 at risk EG0020 affected16 at risk EG003
Hypotension	Vascular disorders	MedDRA (19.0)	Non-systematic Assessment	EG0003 affected8 at risk EG0012 affected4 at risk EG0023 affected16 at risk EG003
Hypertension	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Hot flush	Vascular disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Skin irritation	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0011 affected4 at risk EG0020 affected16 at risk EG003
Bacteraemia	Infections and infestations	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Listeriosis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Oral herpes	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Sepsis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Confusional state	Psychiatric disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Bruxism	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Hallucination	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Incontinence	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Micturition urgency	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (19.0)	Non-systematic Assessment	EG0002 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Bradycardia	Cardiac disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Oedema genital	Reproductive system and breast disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Ear discomfort	Ear and labyrinth disorders	MedDRA (19.0)	Non-systematic Assessment	EG0001 affected8 at risk EG0010 affected4 at risk EG0020 affected16 at risk EG003
Tinnitus	Ear and labyrinth disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Vision blurred	Eye disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0022 affected16 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA (19.0)	Non-systematic Assessment	EG0000 affected8 at risk EG0010 affected4 at risk EG0021 affected16 at risk EG003

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.

Certain Agreements

ID	Term
D010051	Ovarian Neoplasms

Ancestor Terms

ID	Term
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D010049	Ovarian Diseases
D000291	Adnexal Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D005833	Genital Neoplasms, Female
D014565	Urogenital Neoplasms
D000091662	Genital Diseases
D004700	Endocrine System Diseases
D006058	Gonadal Disorders

ID	Term
C000613752	epacadostat
C582435	pembrolizumab

Only 1 subject in the SAF for this study arm; standard deviation could not be calculated

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.

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