Phase 1/2 Study of Mocetinostat and Durvalumab in Patients With Advanced Solid Tumors and NSCLC

NCT02805660 | Terminated Phase 1 Results

• 1 other identifier: 0103-020
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 15

Brief Summary

Mocetinostat (MGCD0103) is an orally administered HDAC inhibitor. Durvalumab (MEDI4736) is a human monoclonal antibody that is an inhibitor of the Programmed Cell Death Ligand (or PD-L1). Durvalumab is also known as a checkpoint inhibitor. This study is evaluating the combination regimen of mocetinostat and durvalumab in participants with Advanced or Metastatic Solid Tumors and Non-Small Cell Lung Cancer.

Conditions

Advanced Cancer

Keywords

MGCD0103; MEDI4736; Mocetinostat; Durvalumab; HDAC Inhibitor; PD-L1 Inhibitor; Phase 1; Phase 2; Metastatic Solid Tumor; Non-small cell lung cancer; immunotherapy; checkpoint inhibitor

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During the First 28-day Cycle of Combination Treatment In Phase 1

  Toxicities were graded using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Any of the following events considered to be causally related to treatment with mocetinostat in combination with durvalumab that occurred during Phase 1 were considered a DLT: * Any Grade 4 immune-related adverse event (irAE) * Grade 3 or greater colitis * Grade 3 or greater noninfectious pneumonitis * Grade 2 pneumonitis that did not resolve to ≤ Grade 1 within 3 days of the initiation of maximal supportive care * Grade 3 irAE (excluding colitis or pneumonitis) that: * Did not resolve to Grade 2 within 3 days after onset of the event despite optimal medical management including systemic corticosteroids, or * Did not resolve to Grade ≤1 or Baseline within 14 days * Liver transaminase elevation \>8×upper limit of normal (ULN) or total bilirubin \>5×ULN * Grade 3 or greater non-irAE, except nausea, vomiting, anorexia, dehydration, or diarrhea

  28 days

• Objective Response Rate (ORR)

  Objective Response Rate (ORR) was defined as the number of participants documented to have a confirmed Complete Response (CR) or Partial Response (PR). Complete Response was defined as the complete disappearance of all target lesions with the exception of nodal disease. Partial Response was defined at least a 30% decrease in the sum of diameters of target measurable lesions. Responses were determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Participants without response data were counted as non-responders. Inferential statistical analyses were conducted for Phase 2 only, as efficacy was not part of the Phase 1 objectives.

  Up to approximately 10 months

Secondary Outcomes (10)

• Number of Participants Experiencing Treatment-Emergent Adverse Events

  Day 1 to 28 days after last dose of study treatment (up to a maximum of 125 weeks in phase 1 and a maximum of 92 weeks in phase 2)

• Duration of Response (DR)

  Up to approximately 10 months

• Clinical Benefit Rate (CBR)

  Up to approximately 10 months

• Progression-Free Survival (PFS)

  Randomization until progressive disease or death due to any cause (up to 42 months)

• 1-Year Survival Rate

  1 year

Study Arms (7)

Phase 1: Dose Escalation - 50 mg

EXPERIMENTAL

The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.

Drug: Mocetinostat - 50 mg; Drug: Durvalumab - 1500 mg

Phase 1: Dose Escalation - 70 mg

EXPERIMENTAL

The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.

Drug: Mocetinostat - 70 mg; Drug: Durvalumab - 1500 mg

Phase 1: Dose Escalation - 90 mg

EXPERIMENTAL

The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.

Drug: Mocetinostat - 90 mg; Drug: Durvalumab - 1500 mg

Phase 2: Combination Regimen - Cohort 1

EXPERIMENTAL

Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort.

Drug: Mocetinostat - Recommended Phase 2 Dose (70 mg); Drug: Durvalumab - 1500 mg

Phase 2: Combination Regimen - Cohort 2

EXPERIMENTAL

Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort.

Drug: Mocetinostat - Recommended Phase 2 Dose (70 mg); Drug: Durvalumab - 1500 mg

Phase 2: Combination Regimen - Cohort 3

EXPERIMENTAL

Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort.

Drug: Mocetinostat - Recommended Phase 2 Dose (70 mg); Drug: Durvalumab - 1500 mg

Phase 2: Combination Regimen - Cohort 4

EXPERIMENTAL

Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort.

Drug: Mocetinostat - Recommended Phase 2 Dose (70 mg); Drug: Durvalumab - 1500 mg

Interventions

Mocetinostat - 50 mg DRUG

Participants received mocetinostat three times weekly as an oral capsule.

Also known as: MGCD0103

Phase 1: Dose Escalation - 50 mg

Mocetinostat - 70 mg DRUG

Participants received mocetinostat three times weekly as an oral capsule.

Also known as: MGCD0103

Phase 1: Dose Escalation - 70 mg

Mocetinostat - 90 mg DRUG

Participants received mocetinostat three times weekly as an oral capsule.

Also known as: MGCD0103

Phase 1: Dose Escalation - 90 mg

Mocetinostat - Recommended Phase 2 Dose (70 mg) DRUG

Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).

Also known as: MGCD0103

Phase 2: Combination Regimen - Cohort 1; Phase 2: Combination Regimen - Cohort 2; Phase 2: Combination Regimen - Cohort 3; Phase 2: Combination Regimen - Cohort 4

Durvalumab - 1500 mg DRUG

Participants received durvalumab as an intravenous infusion every 4 weeks.

Also known as: MEDI4736

Phase 1: Dose Escalation - 50 mg; Phase 1: Dose Escalation - 70 mg; Phase 1: Dose Escalation - 90 mg; Phase 2: Combination Regimen - Cohort 1; Phase 2: Combination Regimen - Cohort 2; Phase 2: Combination Regimen - Cohort 3; Phase 2: Combination Regimen - Cohort 4

Eligibility Criteria

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

You may qualify if:

• Phase 1-Diagnosis of advanced or metastatic solid tumor; Phase 2-Diagnosis of NSCLC
• Not amenable to treatment with curative intent
• Adequate bone marrow and organ function

You may not qualify if:

• Impaired heart function
• Uncontrolled tumor in the brain
• Other active cancer

Sponsors & Collaborators

• Mirati Therapeutics Inc.: lead

Study Sites (15)

Southern Cancer Center, PC

Mobile, Alabama, 36608, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

Woodlands Medical Specialists - Pensacola

Pensacola, Florida, 32503, United States

Location

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

Location

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

Unniversity of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, 55414, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research Centers

Dallas, Texas, 75230, United States

Location

Texas Oncology - Denton South

Denton, Texas, 76210, United States

Location

Texas Oncology-Plano West

Plano, Texas, 75093, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Shenandoah Oncology - Winchester

Winchester, Virginia, 22601, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung

Interventions

mocetinostat; durvalumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

The study was discontinued early because the Sponsor de-prioritized development of mocetinostat. The decision to stop was not due to any patient safety issues.

Results Point of Contact

• Title: Tavette Neskorik, Senior Director, Clinical Science
• Organization: Mirati Therapeutics

neskorikt@mirati.com

858-332-3552

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: June 10, 2016
• First Posted: June 20, 2016
• Study Start: June 1, 2016
• Primary Completion: December 14, 2019
• Study Completion: December 20, 2019
• Last Updated: April 6, 2021
• Results First Posted: April 6, 2021

Record last verified: 2021-03

Locations

US (15)