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

Advanced Cancer Clinical Trial

Official title:

A Phase 1/2 Study of HDAC Inhibitor, Mocetinostat, in Combination With PD-L1 Inhibitor, Durvalumab, in Advanced or Metastatic Solid Tumors and Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02805660
• Other study ID #: 0103-020
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 1, 2016
• Est. completion date: December 20, 2019

Study information

• Verified date: March 2021
• Source: Mirati Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 83
• Est. completion date: December 20, 2019
• Est. primary completion date: December 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Impaired heart function

• Uncontrolled tumor in the brain

• Other active cancer

Related Conditions & MeSH terms

• Advanced Cancer

Intervention

Drug:
• Mocetinostat - 50 mg
Participants received mocetinostat three times weekly as an oral capsule.
• Mocetinostat - 70 mg
Participants received mocetinostat three times weekly as an oral capsule.
• Mocetinostat - 90 mg
Participants received mocetinostat three times weekly as an oral capsule.
• Mocetinostat - Recommended Phase 2 Dose (70 mg)
Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
• Durvalumab - 1500 mg
Participants received durvalumab as an intravenous infusion every 4 weeks.

Locations

Country	Name	City	State
United States	Montefiore Medical Center	Bronx	New York
United States	Robert H. Lurie Comprehensive Cancer Center of Northwestern University	Chicago	Illinois
United States	Mary Crowley Cancer Research Centers	Dallas	Texas
United States	Texas Oncology - Denton South	Denton	Texas
United States	NorthShore University Health System	Evanston	Illinois
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Unniversity of Minnesota Masonic Cancer Center	Minneapolis	Minnesota
United States	Southern Cancer Center, PC	Mobile	Alabama
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Woodlands Medical Specialists - Pensacola	Pensacola	Florida
United States	Texas Oncology-Plano West	Plano	Texas
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Shenandoah Oncology - Winchester	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Mirati Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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)
Secondary	Duration of Response (DR)	DR was defined as the time in days from date of the first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the first documentation of objective Progressive Disease (PD) or to death due to any cause in the absence of documented PD. DR was only calculated for the subgroup of participants who achieved a Best Overall Response of CR or PR and was presented for responses assessed by Investigator's assessment.; Data is displayed for Phase 2 only, as no participants experienced an objective response (CR or PR) during Phase 1.	Up to approximately 10 months
Secondary	Clinical Benefit Rate (CBR)	Clinical benefit rate (CBR) was defined as the number of participants documented to have a confirmed Complete Response (CR), Partial Response (PR), or Stable Disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Participants who were not be able to be assessed for response were counted as non-responders.	Up to approximately 10 months
Secondary	Progression-Free Survival (PFS)	Progression-free survival (PFS) was defined as the time from date of first study treatment to first Progressive Disease (PD) or death due to any cause in the absence of documented PD per RECIST v1.1	Randomization until progressive disease or death due to any cause (up to 42 months)
Secondary	1-Year Survival Rate		1 year
Secondary	Overall Survival (OS)	OS was defined as the time from first dose of study treatment to the date of death due to any cause.	From date of first study treatment until death due to any cause (up to 42 months)
Secondary	Concentration of Mocetinistat in Blood Plasma		Cycle 1 Day 1 pre-dose, 1, 3, and 7 hours post-dose, Cycle 1 Day 15 pre-dose and 1 hour post-dose, Cycle 2 Day 1 pre-dose and 1 hour post-dose, Cycle 3 Day 1 pre-dose and 1 hour post-dose and Cycle 7 Day 1 pre-dose (each cycle is 28 days)
Secondary	Concentration of Durvalumab in Blood Plasma	Plasma concentration of Durvalumab was evaluated. All participants received the same Durvalumab dose regardless of Mocetinistat dose group.	Cycle 1 Day 1 pre-dose + end of infusion, Cycle 1 Day 15 pre-mocetinostat dose, Cycle 2 Day 1 pre-dose, Cycle 3 Day 1 pre-dose, Cycle 4 Day 1 pre-dose + end of infusion, Cycle 7 Day 1 pre-dose + 90 days after participant's last dose (Up to max 133 weeks)
Secondary	Number of Participants With the Presence of Anti-Drug Antibody (ADA) in the Blood		Up to approximately 10 months
Secondary	Number of Participants With Tumor Expression of Programmed Cell Death Ligand 1 (PD-L1) at Baseline		Baseline