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.
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
Interventions
Drug | Synonyms | Arms |
---|
Belvarafenib | | Belvarafenib Monotherapy |
Cobimetinib | | Belvarafenib Plus cobimetinib |
Atezolizumab | Tecentriq | Belvarafenib 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
Name | Type | Description | Interventions |
---|
Belvarafenib Monotherapy | Experimental | Twice daily (BID), continuous dosing. | |
Belvarafenib Plus cobimetinib | Experimental | Recommended 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. | |
Belvarafenib Plus Cobimetinib Plus Atezolizumab | Experimental | Recommended dose (RD) and schedule of belvarafenib and cobimetinib plus atezolizumab IV infusion every 4 weeks (Q4W) followed by an expansion phase | |
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