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

NCT02575807 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: ADU-CL-11
• Study Type: interventional
• Target: 35
• Locations: 2 countries
• Sites: 12

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.

Conditions

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

Keywords

Ovarian cancer; Fallopian cancer; Primary peritoneal cancer

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

• 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.

  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.

Secondary Outcomes (5)

• 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.

• 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

• 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.

• 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.

• 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.

Study Arms (5)

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.

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

Phase 2: CRS-207/Pembro

EXPERIMENTAL

CRS-207 and pembro administered in 3-week cycles. * CRS-207 (1 x 10e9 CFU) administered by IV infusion. For Cycle 1 through Cycle 6, CRS-207 administered on Day 2 of each cycle. After 6 cycles, CRS-207 administered on Day 2 once every 6 weeks (every other cycle). * Pembro (200 mg) administered by IV infusion on Day 1 in 3-week cycles.

Biological: CRS-207; Biological: Pembrolizumab

Interventions

CRS-207 BIOLOGICAL

via IV infusion

Also known as: Live, attenuated double-deleted Listeria monocytogenes (LADD)

Phase 1: CRS-207; Phase 1: CRS-207/IDO 100 mg; Phase 1: CRS-207/IDO 300 mg; Phase 2: CRS-207/Pembro; Phase 2: CRS-207/Pembro/IDO

Epacadostat DRUG

PO BID

Also known as: INCB024360, IDO

Phase 1: CRS-207/IDO 100 mg; Phase 1: CRS-207/IDO 300 mg; Phase 2: CRS-207/Pembro/IDO

Pembrolizumab BIOLOGICAL

via IV infusion

Also known as: Keytruda®, Pembro

Phase 2: CRS-207/Pembro; Phase 2: CRS-207/Pembro/IDO

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aduro Biotech, Inc.: lead
• Incyte Corporation: collaborator

Study Sites (12)

Scottsdale Healthcare Hospitals DBA HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM - Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2X 0A9, Canada

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

epacadostat; pembrolizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Limitations and Caveats

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

Results Point of Contact

• Title: Medical Affairs
• Organization: Aduro Biotech, Inc.

MedicalAffairs@aduro.com

510.809.2452

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 15, 2015
• Study Start: March 8, 2016
• Primary Completion: April 26, 2018
• Study Completion: May 8, 2018
• Last Updated: April 4, 2019
• Results First Posted: April 4, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (10)