Study of Avelumab With or Without Entinostat in Participants With Advanced Epithelial Ovarian Cancer

NCT ID: NCT02915523

Last Updated: 2024-01-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-19

Study Completion Date

2021-04-21

Brief Summary

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The purpose of this study is to determine the biologically active dose of entinostat, when given in combination with avelumab, that is safe and warrants further investigation. Additionally, this study will evaluate the effectiveness of entinostat in combination with avelumab at the determined dose in terms of progression free survival compared to avelumab plus placebo in participants with refractory or recurrent epithelial ovarian cancer.

Detailed Description

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The study is comprised of 2 phases: an open-label Safety Lead-in (Phase 1b) followed by an Expansion Phase (Phase 2). The Expansion Phase will evaluate the efficacy and safety of entinostat with avelumab when administered at the Recommended Phase 2 Dose (RP2D) versus avelumab alone in participants with advanced epithelial ovarian cancer in a randomized, double-blind, placebo-controlled setting. In Phase 2, participants will be randomized in a 2:1 ratio to receive avelumab plus entinostat or avelumab plus placebo, respectively.

All participants will be assessed at Screening and at specified times during the conduct of the study using standard clinical and laboratory assessments. Participants will be assessed for response through radiological assessments. Participants will continue receiving their appropriate cycles of study treatment until tumor progression or adverse events (AEs) occur which necessitate discontinuing therapy as determined by the Investigator.

Conditions

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Epithelial Ovarian Cancer Peritoneal Cancer Fallopian Tube Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Entinostat plus Avelumab

Avelumab is administered intravenously (IV) on Day 1 of each 14-day cycle in combination with Entinostat administration on Day 1 and Day 8 of each cycle at the Maximum tolerated Dose (MTD)/RP2D as determined in the Phase Ib (Dose Determination) part of the study.

Group Type ACTIVE_COMPARATOR

entinostat

Intervention Type DRUG

An orally available histone deacetylases inhibitor (HDACi).

avelumab

Intervention Type DRUG

A fully human antibody of the immunoglobulin (Ig) G1 isotype that targets and blocks Programmed death-ligand 1 (PD-L1), the ligand for Programmed cell death protein 1 (PD-1) receptor.

Placebo plus Avelumab

Avelumab is administered intravenously (IV) on Day 1 of each 14-day cycle in combination with placebo administered on Day 1 and Day 8 of each cycle.

Group Type PLACEBO_COMPARATOR

avelumab

Intervention Type DRUG

A fully human antibody of the immunoglobulin (Ig) G1 isotype that targets and blocks Programmed death-ligand 1 (PD-L1), the ligand for Programmed cell death protein 1 (PD-1) receptor.

Placebo

Intervention Type DRUG

A pill containing no active drug ingredient.

Interventions

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entinostat

An orally available histone deacetylases inhibitor (HDACi).

Intervention Type DRUG

avelumab

A fully human antibody of the immunoglobulin (Ig) G1 isotype that targets and blocks Programmed death-ligand 1 (PD-L1), the ligand for Programmed cell death protein 1 (PD-1) receptor.

Intervention Type DRUG

Placebo

A pill containing no active drug ingredient.

Intervention Type DRUG

Other Intervention Names

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SNDX-275 MS-275 MSB0010718C

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer
* Recurrent or progressive disease on or after initial platinum-based chemotherapy
* Evidence of measurable disease based on imaging studies within 28 days before the first dose of study drug
* Previously received at least 3, but no more than 6, lines of therapy including at least 1 course of platinum-based therapy
* Participant must have acceptable, applicable laboratory requirements
* Participants may have a history of brain metastasis provided certain protocol criteria are met
* Experienced resolution of toxic effect(s) of the most recent prior anti-cancer therapy to Grade ≤1 (except alopecia or neuropathy)
* Able to understand and give written informed consent and comply with study procedures.

Exclusion Criteria

* Non-epithelial ovarian carcinomas or ovarian tumors with low malignant potential (i.e., borderline tumors)
* Another known malignancy that is progressing or requires active treatment (excluding adequately treated basal cell carcinoma or cervical intraepithelial neoplasia/cervical carcinoma in situ or melanoma in situ). Prior history of other cancer is allowed, as long as there is no active disease within the prior 5 years.
* Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment.
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* Previously treated with a histone deacetylase inhibitor (i.e., vorinostat, belinostat, romidepsin, panobinostat), PD-1/PD-L1-blocking antibody (i.e., atezolizumab, nivolumab, pembrolizumab), or a cytotoxic T-lymphocyte associated protein-4 (CTLA-4) agent
* Currently enrolled in (or completed) another investigational drug study within 30 days prior to study drug administration
* A medical condition that precludes adequate study treatment or increases participant risk
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role collaborator

Syndax Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Meyers, MD, PhD

Role: STUDY_DIRECTOR

Syndax Pharmaceuticals

Ursula Matulonis, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

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H. Lee Moffitt Cancer Center and Research

Tampa, Florida, United States

Site Status

Florida Cancer Specialist East Region (SCRI Affiliate)

West Palm Beach, Florida, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

HCA Midwest Health (SCRI Affiliate)

Kansas City, Missouri, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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SNDX-275-0603

Identifier Type: -

Identifier Source: org_study_id

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