A Study of Cobimetinib Administered as Single Agent and in Combination With Venetoclax, With or Without Atezolizumab, in Participants With Relapsed and Refractory Multiple Myeloma

Sponsor
Hoffmann-La Roche
Study ID
NCT03312530
Phase
PHASE1/PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Cobimetinib — DRUG
    Cobimetinib will be administered as per the schedule specified in the respective arm.
  • Venetoclax — DRUG
    Venetoclax will be administered as per the schedule specified in the respective arm.
  • Atezolizumab — DRUG
    Atezolizumab will be administered as per the schedule specified in the respective arm.

Study Details

This open-label, randomized, multicenter, triple-arm Phase Ib/II study is designed to assess the efficacy, safety, tolerability, and pharmacokinetics of cobimetinib administered as a single agent (Arm A), cobimetinib plus venetoclax (Arm B), and cobimetinib plus venetoclax plus atezolizumab (Arm C) in participants with relapsed and refractory multiple myeloma. Two successive cohorts will evaluate the safety of cobimetinib plus venetoclax and that of cobimetinib plus venetoclax plus atezolizumab in the selected population during the safety run-in phase of the study. Once the dose levels have demonstrated acceptable safety during this phase, randomization will begin for all treatment arms (Arms A, B, and C).

Key Dates

Start date
Nov 13, 2017
Status verified
Feb 2023
Primary completion
May 18, 2021
Completion
May 18, 2021

Study Design

Enrollment
49 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: A: Cobimetinib
    Participants will receive the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants will be allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment will continue until the participant has disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
  • Experimental: B: Cobimetinib + Venetoclax
    Participants will receive cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment will continue until the participant has disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
  • Experimental: C: Cobimetinib + Venetoclax + Atezolizumab
    Participants will receive cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment will continue until the participant has disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
  • Experimental: Safety Run-In: Cobimetinib + Venetoclax
    Participants will receive cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
  • Experimental: Safety Run-In: Cobimetinib + Venetoclax + Atezolizumab
    Participants will receive cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.

Primary Outcome Measure

Percentage of Participants With Adverse Events (AEs) [ Time Frame: Randomization up to end of study (up to approximately 3 years, 7 months) ]

Related Studies