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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04835805




Registration number
NCT04835805
Ethics application status
Date submitted
6/04/2021
Date registered
8/04/2021
Date last updated
16/05/2024

Titles & IDs
Public title
A Study to Evaluate the Safety and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Nivolumab in Patients With NRAS-mutant Advanced Melanoma.
Scientific 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 Nivolumab in Patients With NRAS-Mutant Advanced Melanoma Who Have Received Anti-PD-1/PD-L1 Therapy
Secondary ID [1] 0 0
2020-003674-41
Secondary ID [2] 0 0
GO42273
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Belvarafenib
Treatment: Drugs - Cobimetinib
Treatment: Drugs - Nivolumab

Experimental: Belvarafenib Monotherapy - Twice daily (BID), continuous dosing.

Experimental: Belvarafenib Plus Cobimetinib - 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.

Experimental: Belvarafenib Plus Cobimetinib Plus Nivolumab - Recommended dose (RD) and schedule of belvarafenib and cobimetinib plus nivolumab IV infusion every 4 weeks (Q4W) in a run-in phase followed by an expansion phase


Treatment: Drugs: Belvarafenib
Twice daily (BID), continuous dosing

Treatment: Drugs: Cobimetinib
Once daily (QD) or three times weekly (TIW) for 21 days, 7 days off

Treatment: Drugs: Nivolumab
Once every 4 weeks (Q4W)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Dose Limiting Toxicity (DLTs)
Timepoint [1] 0 0
28 Days from Cycle 1, Day 1
Primary outcome [2] 0 0
Percentage of Participants With Adverse Events
Timepoint [2] 0 0
From Cycle 1, Day 1 Up to 4 Years
Secondary outcome [1] 0 0
Objective response rate (ORR) according to RECIST v1.1
Timepoint [1] 0 0
Up to Approximately 4 Years
Secondary outcome [2] 0 0
Progression free survival (PFS) according to RECIST v1.1
Timepoint [2] 0 0
Up to Approximately 4 Years
Secondary outcome [3] 0 0
Duration of response (DOR) according to RECIST v1.1
Timepoint [3] 0 0
Up to Approximately 4 Years
Secondary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
Up to Approximately 4 Years
Secondary outcome [5] 0 0
Plasma concentration of belvarafenib at specified timepoints
Timepoint [5] 0 0
Up to 30 Days After the Final Dose of Study Drug
Secondary outcome [6] 0 0
Plasma concentration of cobimetinib at specified timepoints
Timepoint [6] 0 0
Up to 30 Days After the Final Dose of Study Drug

Eligibility
Key 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 progressed 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior treatment with a pan-RAF inhibitor

- 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 (nivolumab arm)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/11/2025
Actual
Sample size
Target
Accrual to date
Final
65
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre-East Melbourne - Melbourne
Recruitment hospital [3] 0 0
Linear Clinical Research Ltd - Nedlands
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
Germany
State/province [10] 0 0
Berlin
Country [11] 0 0
Germany
State/province [11] 0 0
Hamburg
Country [12] 0 0
Germany
State/province [12] 0 0
Mannheim
Country [13] 0 0
Germany
State/province [13] 0 0
Tübingen
Country [14] 0 0
Germany
State/province [14] 0 0
Würzburg
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul
Country [16] 0 0
Norway
State/province [16] 0 0
Bergen
Country [17] 0 0
Norway
State/province [17] 0 0
Oslo

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the safety, pharmacokinetics, and activity of belvarafenib as a
single agent and in combination with either cobimetinib or cobimetinib plus nivolumab in
patients with NRAS-mutant advanced melanoma who have received anti-PD-1/PD-L1 therapy.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04835805
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04835805