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.
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.
Brief Title
Phase 1/2 Study of Mocetinostat and Durvalumab in Patients With Advanced Solid Tumors and NSCLC
Completion Date
Completion Date Type
Actual
Conditions
Advanced Cancer
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02805660
Org Class
Industry
Org Full Name
Mirati Therapeutics Inc.
Org Study Id
0103-020
Overall Status
Terminated
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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
* 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
Outcome Measure
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During the First 28-day Cycle of Combination Treatment In Phase 1
Outcome Time Frame
28 days
Outcome Description
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.
Inferential statistical analyses were conducted for Phase 2 only, as efficacy was not part of the Phase 1 objectives.
Outcome Measure
Objective Response Rate (ORR)
Outcome Time Frame
Up to approximately 10 months
Secondary Outcomes
Outcome 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)
Outcome Measure
Number of Participants Experiencing Treatment-Emergent Adverse Events
Outcome Description
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.
Data is displayed for Phase 2 only, as no participants experienced an objective response (CR or PR) during Phase 1.
Outcome Time Frame
Up to approximately 10 months
Outcome Measure
Duration of Response (DR)
Outcome Description
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.
Outcome Time Frame
Up to approximately 10 months
Outcome Measure
Clinical Benefit Rate (CBR)
Outcome Description
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
Outcome Time Frame
Randomization until progressive disease or death due to any cause (up to 42 months)
Outcome Measure
Progression-Free Survival (PFS)
Outcome Time Frame
1 year
Outcome Measure
1-Year Survival Rate
Outcome Description
OS was defined as the time from first dose of study treatment to the date of death due to any cause.
Outcome Time Frame
From date of first study treatment until death due to any cause (up to 42 months)
Outcome Measure
Overall Survival (OS)
Outcome 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)
Outcome Measure
Concentration of Mocetinistat in Blood Plasma
Outcome Description
Plasma concentration of Durvalumab was evaluated. All participants received the same Durvalumab dose regardless of Mocetinistat dose group.
Outcome 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)
Outcome Measure
Concentration of Durvalumab in Blood Plasma
Outcome Time Frame
Up to approximately 10 months
Outcome Measure
Number of Participants With the Presence of Anti-Drug Antibody (ADA) in the Blood
Outcome Time Frame
Baseline
Outcome Measure
Number of Participants With Tumor Expression of Programmed Cell Death Ligand 1 (PD-L1) at Baseline
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Phone
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Cancer --- NEOPLASMS
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
NEOPLASM METASTASIS
CARCINOMA, NON-SMALL-CELL LUNG
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
MOCETINOSTAT
DURVALUMAB