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

Aduro Biotech

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Platinum-resistant Fallopian Cancer; Platinum-resistant Peritoneal Cancer; Platinum-resistant Ovarian Cancer

Treatments: Biological: Pembrolizumab; Drug: Epacadostat; Biological: CRS-207

Study type: Interventional

Funder types: Industry

Identifiers

NCT02575807

ADU-CL-11

Details and patient eligibility

About

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.

Enrollment: 35 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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35 participants in 5 patient groups

Phase 1: CRS-207

Experimental 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).

Treatment:

Biological: CRS-207

Phase 1: CRS-207/IDO 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Epacadostat

Biological: CRS-207

Phase 1: CRS-207/IDO 300 mg

Experimental group

Description:

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.

Treatment:

Drug: Epacadostat

Biological: CRS-207

Phase 2: CRS-207/Pembro/IDO

Experimental group

Description:

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.

Treatment:

Drug: Epacadostat

Biological: CRS-207

Biological: Pembrolizumab

Phase 2: CRS-207/Pembro

Experimental group

Description:

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.

Treatment:

Biological: CRS-207

Biological: Pembrolizumab