Clinical Trial 19184

Cancer Type:
Interventions:Avelumab; Entinostat; MSB00100718C (Avelumab); Not Applicable; Placebo

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Robert Wenham

Overview

Study Title

A Randomized, Placebo-controlled, Double-blind, Multicenter Phase 1b/2 Study of Avelumab With or Without Entinostat in Patients with Advanced Epithelial Ovarian Cancer Which Has Progressed or Recurred After First-line Platinum-based Chemotherapy and at Least Two Subsequent Lines of Treatment with a Safety Lead-in [SNDX-275-0603]

Summary

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 patients with refractory or recurrent epithelial ovarian cancer.

Objective

Primary Objective: Phase 1b: (Safety lead-in): To determine the dose-limiting toxicities (DLTs) and maximum-tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of entinostat (SNDX-275) given in combination with avelumab. Phase 2 (Expansion Phase): To perform an evaluation of the efficacy of entinostat in combination with avelumab at the RP2D versus avelumab plus placebo in patients with refractory or recurrent epithelial ovarian cancer, as determined by the duration of progression-free survival (PFS) based on the local investigator's assessment of progressive disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Secondary Objectives: Efficacy: To evaluate the efficacy of entinostat in combination with avelumab in patients with advanced epithelial ovarian cancer, as determined by: PFS based on immune response RECIST (irRECIST); Overall response rate (ORR) (i.e., complete response [CR] or partial response [PR]) based on RECIST 1.1 and irRECIST; Clinical benefit rate (CBR) (i.e., CR or PR or stable disease [SD] for at least 24 weeks) based on RECIST 1.1 and irRECIST; Overall survival (OS).

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
  • Participants must have acceptable, applicable laboratory requirements
  • 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 patient risk