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

Purpose

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.

Condition

  • Advanced Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1: Dose Escalation - 50 mg 		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
    Participants received mocetinostat three times weekly as an oral capsule.
    Other names:
    • MGCD0103
  • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other names:
    • MEDI4736
Experimental
Phase 1: Dose Escalation - 70 mg 		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
    Participants received mocetinostat three times weekly as an oral capsule.
    Other names:
    • MGCD0103
  • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other names:
    • MEDI4736
Experimental
Phase 1: Dose Escalation - 90 mg 		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
    Participants received mocetinostat three times weekly as an oral capsule.
    Other names:
    • MGCD0103
  • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other names:
    • MEDI4736
Experimental
Phase 2: Combination Regimen - Cohort 1 		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)
    Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Other names:
    • MGCD0103
  • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other names:
    • MEDI4736
Experimental
Phase 2: Combination Regimen - Cohort 2 		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)
    Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Other names:
    • MGCD0103
  • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other names:
    • MEDI4736
Experimental
Phase 2: Combination Regimen - Cohort 3 		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)
    Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Other names:
    • MGCD0103
  • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other names:
    • MEDI4736
Experimental
Phase 2: Combination Regimen - Cohort 4 		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)
    Participants received mocetinostat three times weekly as an oral capsule, at the dose recommended after Phase 1 (70 mg).
    Other names:
    • MGCD0103
  • Drug: Durvalumab - 1500 mg
    Participants received durvalumab as an intravenous infusion every 4 weeks.
    Other names:
    • MEDI4736

More Details

Status
Terminated
Sponsor
Mirati Therapeutics Inc.

Study Contact