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A Study to Evaluate the Safety and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Atezolizumab in Patients With NRAS-mutant Advanced Melanoma.

NCT04835805

Description:

This study will evaluate the safety, pharmacokinetics, and activity of belvarafenib as a single agent and in combination with either cobimetinib or cobimetinib plus atezolizumab in patients with NRAS-mutant advanced melanoma who have received anti-PD-1/PD-L1 therapy.

Related Conditions:
  • Cutaneous Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Atezolizumab in Patients With NRAS-mutant Advanced Melanoma.
  • Official Title: A Phase Ib, Open-Label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Atezolizumab in Patients With NRAS-Mutant Advanced Melanoma Who Have Received Anti-PD-1/PD-L1 Therapy

Clinical Trial IDs

  • ORG STUDY ID: GO42273
  • SECONDARY ID: 2020-003674-41
  • NCT ID: NCT04835805

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
BelvarafenibBelvarafenib Monotherapy
CobimetinibBelvarafenib Plus cobimetinib
AtezolizumabTecentriqBelvarafenib Plus Cobimetinib Plus Atezolizumab

Purpose

This study will evaluate the safety, pharmacokinetics, and activity of belvarafenib as a single agent and in combination with either cobimetinib or cobimetinib plus atezolizumab in patients with NRAS-mutant advanced melanoma who have received anti-PD-1/PD-L1 therapy.

Detailed Description

      The study will evaluate three treatment regimens in three arms: a belvarafenib monotherapy
      arm (Belva arm) of up to 15 patients; a belvarafenib plus cobimetinib arm (Belva + Cobi arm)
      in an initial dose-finding phase followed by an expansion phase and a belvarafenib plus
      cobimetinib plus atezolizumab arm (Belva + Cobi + Atezo arm) in a run-in phase followed by an
      expansion phase.
    

Trial Arms

NameTypeDescriptionInterventions
Belvarafenib MonotherapyExperimentalTwice daily (BID), continuous dosing.
  • Belvarafenib
Belvarafenib Plus cobimetinibExperimentalRecommended dose (RD) and schedule of belvarafenib and cobimetinib selected based on the safety data, tolerability, pharmacokinetics, and anti-tumor activity tested in dose-finding phase followed by an expansion phase.
  • Cobimetinib
Belvarafenib Plus Cobimetinib Plus AtezolizumabExperimentalRecommended dose (RD) and schedule of belvarafenib and cobimetinib plus atezolizumab IV infusion every 4 weeks (Q4W) followed by an expansion phase
  • Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  ECOG Performance Status of 0 or 1

          -  Histologically confirmed, metastatic (recurrent or de novo Stage IV) or unresectable
             locally advanced (Stage III) cutaneous melanoma, that has progressed on or after
             treatment with anti-PD-1 or anti-PD-L1 therapy. Patients may have received up to two
             lines of systemic cancer therapy. Treatment with anti-PD-1/PD-L1 in the adjuvant
             setting is acceptable. Patients must have progressive disease at study entry

          -  Documentation of NRAS mutation-positive within 5 years prior to screening

          -  Tumor specimen availability

          -  Adequate hematologic and end-organ function

          -  Measurable disease per RECIST v1.1

        Exclusion Criteria:

          -  Treatment with systemic immunotherapy agents (e.g., anti-CTLA4, anti-PD(L)1, cytokine
             therapy, investigational therapy, etc.) within 28 days prior to C1D1

          -  Symptomatic, untreated, or actively progressing CNS metastases

          -  History or signs/symptoms of clinically significant cardiovascular disease

          -  Known clinically significant liver disease

          -  History of autoimmune disease or immune deficiency

          -  Prior treatment with a MEK inhibitor (cobimetinib arm)

          -  History of or evidence of retinal pathology on ophthalmologic examination (cobimetinib
             arm)

          -  History of immune-related AE attributed to prior anti-PD(L)1 therapy that resulted in
             permanent discontinuation of anti-PD(L)1 therapy (atezolizumab arm)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Dose Limiting Toxicity (DLTs)
Time Frame:28 Days from Cycle 1, Day 1
Safety Issue:
Description:Severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0

Secondary Outcome Measures

Measure:Objective response rate (ORR) according to RECIST v1.1
Time Frame:Up to Approximately 4 Years
Safety Issue:
Description:Defined as the percentage of participants with a CR or PR on two consecutive occasions >/= 4 weeks apart, as determined by the investigator according to RECIST v1.1
Measure:Progression free survival (PFS) according to RECIST v1.1
Time Frame:Up to Approximately 4 Years
Safety Issue:
Description:Defined as the time from the first study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
Measure:Duration of response (DOR) according to RECIST v1.1
Time Frame:Up to Approximately 4 Years
Safety Issue:
Description:Defined as the time from the first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
Measure:Overall survival (OS)
Time Frame:Up to Approximately 4 Years
Safety Issue:
Description:Defined as the time from the first study treatment to death from any cause
Measure:Plasma concentration of belvarafenib at specified timepoints
Time Frame:Up to 30 Days After the Final Dose of Study Drug
Safety Issue:
Description:
Measure:Plasma concentration of cobimetinib at specified timepoints
Time Frame:Up to 30 Days After the Final Dose of Study Drug
Safety Issue:
Description:
Measure:Serum concentration of atezolizumab at specified timepoints
Time Frame:Up to 30 Days After the Final Dose of Study Drug
Safety Issue:
Description:
Measure:Concentration of atezolizumab anti-drug antibody (ADA)
Time Frame:Up to 30 Days After the Final Dose of Study Drug
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genentech, Inc.

Last Updated

August 27, 2021