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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
83
Participants received mocetinostat three times weekly as an oral capsule.
Participants received mocetinostat three times weekly as an oral capsule.
Participants received mocetinostat three times weekly as an oral capsule.
Southern Cancer Center, PC
Mobile, Alabama, United States
David Geffen School of Medicine at UCLA
Los Angeles, California, United States
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
Time frame: 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.
Time frame: Up to approximately 10 months
Number of Participants Experiencing Treatment-Emergent Adverse Events
Time frame: 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)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
Participants received durvalumab as an intravenous infusion every 4 weeks.
Woodlands Medical Specialists - Pensacola
Pensacola, Florida, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, United States
NorthShore University Health System
Evanston, Illinois, United States
Unniversity of Minnesota Masonic Cancer Center
Minneapolis, Minnesota, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Montefiore Medical Center
The Bronx, New York, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Mary Crowley Cancer Research Centers
Dallas, Texas, United States
...and 5 more locations
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.
Time frame: Up to approximately 10 months
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.
Time frame: Up to approximately 10 months
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
Time frame: Randomization until progressive disease or death due to any cause (up to 42 months)
1-Year Survival Rate
Time frame: 1 year
Overall Survival (OS)
OS was defined as the time from first dose of study treatment to the date of death due to any cause.
Time frame: From date of first study treatment until death due to any cause (up to 42 months)
Concentration of Mocetinistat in Blood Plasma
Time frame: 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)
Concentration of Durvalumab in Blood Plasma
Plasma concentration of Durvalumab was evaluated. All participants received the same Durvalumab dose regardless of Mocetinistat dose group.
Time frame: 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)
Number of Participants With the Presence of Anti-Drug Antibody (ADA) in the Blood
Time frame: Up to approximately 10 months
Number of Participants With Tumor Expression of Programmed Cell Death Ligand 1 (PD-L1) at Baseline
Time frame: Baseline