Platinum-resistant Ovarian Cancer, Platinum-resistant Fallopian Cancer, Platinum-resistant Peritoneal Cancer
Conditions
Keywords
Ovarian cancer, Fallopian cancer, Primary peritoneal cancer
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.
Interventions
Sponsors
Incyte Corporation
Aduro Biotech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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). 2. Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 3. Agree to provide core biopsies at baseline and at Cycle 2 Day 15 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 5. Available archived tumor tissue for central analysis 6. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 |
| 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. | 4 |
| 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. | 16 |
| 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 |
| 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. | 3 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 8 | 3 | 7 | 0 | 1 |
| Overall Study | Study terminated by Sponsor | 0 | 1 | 7 | 0 | 1 |
| Overall Study | Subject ineligible - medical implant | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Terminated due to FDA clinical hold | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Terminated due to physician decision | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Phase 1: CRS-207 | Total | Phase 2: CRS-207/Pembro | Phase 2: CRS-207/Pembro/IDO | Phase 1: CRS-207/IDO 300 mg | Phase 1: CRS-207/IDO 100 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 61.1 years STANDARD_DEVIATION 11.03 | 61.9 years STANDARD_DEVIATION 9.39 | 61.7 years STANDARD_DEVIATION 5.13 | 60.0 years | 62.4 years STANDARD_DEVIATION 9.35 | 62.0 years STANDARD_DEVIATION 12.99 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 30 Participants | 3 Participants | 1 Participants | 15 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 29 Participants | 2 Participants | 1 Participants | 15 Participants | 3 Participants |
| Region of Enrollment Canada | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Region of Enrollment United States | 8 Participants | 30 Participants | 3 Participants | 1 Participants | 14 Participants | 4 Participants |
| Sex: Female, Male Female | 8 Participants | 32 Participants | 3 Participants | 1 Participants | 16 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 8 | 3 / 4 | 7 / 16 | 1 / 1 | 1 / 3 |
| other Total, other adverse events | 8 / 8 | 4 / 4 | 16 / 16 | 1 / 1 | 3 / 3 |
| serious Total, serious adverse events | 2 / 8 | 1 / 4 | 9 / 16 | 1 / 1 | 1 / 3 |
Outcome results
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.
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.
Population: Analysis performed on subjects in the Phase 1 safety analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: CRS-207 | Phase 1: Adverse Events (AEs) by CTCAE Grade 3 or Higher | 6 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 1: Adverse Events (AEs) by CTCAE Grade 3 or Higher | 3 Participants |
| Phase 1: CRS-207/IDO 300 mg | Phase 1: Adverse Events (AEs) by CTCAE Grade 3 or Higher | 14 Participants |
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.
Time frame: Subjects followed for DLTs for 21 days following the first dose of CRS-207 (treatment Cycle 1 for CRS-207).
Population: Analysis performed on subjects in the Phase 1 safety analysis set (SAF).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: CRS-207 | Phase 1: Number of Subjects Reporting Hematologic and/or Non-hematologic Dose-limiting Toxicity (DLT) | 1 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 1: Number of Subjects Reporting Hematologic and/or Non-hematologic Dose-limiting Toxicity (DLT) | 0 Participants |
| Phase 1: CRS-207/IDO 300 mg | Phase 1: Number of Subjects Reporting Hematologic and/or Non-hematologic Dose-limiting Toxicity (DLT) | 1 Participants |
Primary
Phase 2: Adverse Events (AEs)
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.
Population: Analysis performed on subjects in the Phase 2 safety analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: CRS-207 | Phase 2: Adverse Events (AEs) | 1 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 2: Adverse Events (AEs) | 3 Participants |
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.
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.
Population: 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 | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: CRS-207 | Phase 2: Objective Response Rate (ORR) | Stable Disease | 0 Participants |
| Phase 1: CRS-207 | Phase 2: Objective Response Rate (ORR) | Progressive Disease | 1 Participants |
| Phase 1: CRS-207 | Phase 2: Objective Response Rate (ORR) | Not Evaluable | 0 Participants |
| Phase 1: CRS-207 | Phase 2: Objective Response Rate (ORR) | Complete Response | 0 Participants |
| Phase 1: CRS-207 | Phase 2: Objective Response Rate (ORR) | Partial Response | 0 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 2: Objective Response Rate (ORR) | Partial Response | 0 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 2: Objective Response Rate (ORR) | Complete Response | 0 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 2: Objective Response Rate (ORR) | Progressive Disease | 2 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 2: Objective Response Rate (ORR) | Stable Disease | 0 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 2: Objective Response Rate (ORR) | Not Evaluable | 0 Participants |
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.
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.
Population: Analysis performed on subjects in the Phase 2 SAF.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: CRS-207 | Phase 2: Progression Free Survival (PFS) | 5.71 weeks |
| Phase 1: CRS-207/IDO 100 mg | Phase 2: Progression Free Survival (PFS) | 7.36 weeks |
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.
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.
Population: Analysis performed on subjects in the Phase 1 and Phase 2 SAF.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: CRS-207 | Disease Control Rate (DCR) | Partial Response (PR) | 0 Participants |
| Phase 1: CRS-207 | Disease Control Rate (DCR) | Complete Response (CR) | 0 Participants |
| Phase 1: CRS-207 | Disease Control Rate (DCR) | Stable Disease (SD) | 1 Participants |
| Phase 1: CRS-207/IDO 100 mg | Disease Control Rate (DCR) | Complete Response (CR) | 0 Participants |
| Phase 1: CRS-207/IDO 100 mg | Disease Control Rate (DCR) | Stable Disease (SD) | 1 Participants |
| Phase 1: CRS-207/IDO 100 mg | Disease Control Rate (DCR) | Partial Response (PR) | 0 Participants |
| Phase 1: CRS-207/IDO 300 mg | Disease Control Rate (DCR) | Complete Response (CR) | 0 Participants |
| Phase 1: CRS-207/IDO 300 mg | Disease Control Rate (DCR) | Partial Response (PR) | 0 Participants |
| Phase 1: CRS-207/IDO 300 mg | Disease Control Rate (DCR) | Stable Disease (SD) | 4 Participants |
| Phase 2: CRS-207/Pembro/IDO | Disease Control Rate (DCR) | Stable Disease (SD) | 0 Participants |
| Phase 2: CRS-207/Pembro/IDO | Disease Control Rate (DCR) | Complete Response (CR) | 0 Participants |
| Phase 2: CRS-207/Pembro/IDO | Disease Control Rate (DCR) | Partial Response (PR) | 0 Participants |
| Phase 2: CRS-207/Pembro | Disease Control Rate (DCR) | Partial Response (PR) | 0 Participants |
| Phase 2: CRS-207/Pembro | Disease Control Rate (DCR) | Complete Response (CR) | 0 Participants |
| Phase 2: CRS-207/Pembro | Disease Control Rate (DCR) | Stable Disease (SD) | 0 Participants |
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.
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.
Population: No study subjects achieved CR or PR designation; therefore, per the final SAP DOR was not derived.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: CRS-207 | Duration of Response (DOR) | 0 Participants |
| Phase 1: CRS-207/IDO 100 mg | Duration of Response (DOR) | 0 Participants |
| Phase 1: CRS-207/IDO 300 mg | Duration of Response (DOR) | 0 Participants |
| Phase 2: CRS-207/Pembro/IDO | Duration of Response (DOR) | 0 Participants |
| Phase 2: CRS-207/Pembro | Duration of Response (DOR) | 0 Participants |
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.
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.
Population: Analysis performed on subjects in the Phase 1 and Phase 2 SAF.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: CRS-207 | Overall Survival (OS) | 49.07 weeks |
| Phase 1: CRS-207/IDO 100 mg | Overall Survival (OS) | 30.00 weeks |
| Phase 1: CRS-207/IDO 300 mg | Overall Survival (OS) | 27.00 weeks |
| Phase 2: CRS-207/Pembro/IDO | Overall Survival (OS) | 9.29 weeks |
| Phase 2: CRS-207/Pembro | Overall Survival (OS) | 18.43 weeks |
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.
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.
Population: 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 | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1: CRS-207 | Phase 1: Objective Response Rate (ORR) by mRECIST | Progressive Disease | 7 Participants |
| Phase 1: CRS-207 | Phase 1: Objective Response Rate (ORR) by mRECIST | Stable Disease | 1 Participants |
| Phase 1: CRS-207 | Phase 1: Objective Response Rate (ORR) by mRECIST | Complete Response | 0 Participants |
| Phase 1: CRS-207 | Phase 1: Objective Response Rate (ORR) by mRECIST | Partial Response | 0 Participants |
| Phase 1: CRS-207 | Phase 1: Objective Response Rate (ORR) by mRECIST | Not Evaluable | 0 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 1: Objective Response Rate (ORR) by mRECIST | Stable Disease | 1 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 1: Objective Response Rate (ORR) by mRECIST | Complete Response | 0 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 1: Objective Response Rate (ORR) by mRECIST | Partial Response | 0 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 1: Objective Response Rate (ORR) by mRECIST | Progressive Disease | 3 Participants |
| Phase 1: CRS-207/IDO 100 mg | Phase 1: Objective Response Rate (ORR) by mRECIST | Not Evaluable | 0 Participants |
| Phase 1: CRS-207/IDO 300 mg | Phase 1: Objective Response Rate (ORR) by mRECIST | Not Evaluable | 3 Participants |
| Phase 1: CRS-207/IDO 300 mg | Phase 1: Objective Response Rate (ORR) by mRECIST | Progressive Disease | 6 Participants |
| Phase 1: CRS-207/IDO 300 mg | Phase 1: Objective Response Rate (ORR) by mRECIST | Complete Response | 0 Participants |
| Phase 1: CRS-207/IDO 300 mg | Phase 1: Objective Response Rate (ORR) by mRECIST | Stable Disease | 4 Participants |
| Phase 1: CRS-207/IDO 300 mg | Phase 1: Objective Response Rate (ORR) by mRECIST | Partial Response | 0 Participants |
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.
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
Population: Analysis performed on subjects in the Phase 1 SAF.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: CRS-207 | Phase 1: Progression Free Survival (PFS) | 8.43 weeks |
| Phase 1: CRS-207/IDO 100 mg | Phase 1: Progression Free Survival (PFS) | 4.71 weeks |
| Phase 1: CRS-207/IDO 300 mg | Phase 1: Progression Free Survival (PFS) | 8.43 weeks |