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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04835805
Ethics application status
Date submitted
6/04/2021
Date registered
8/04/2021

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/study/NCT04835805
Trial related presentations / publications
Moschos SJ. War against NRAS-Mutant Melanoma Using Targeted Therapies Remains Challenging. Clin Cancer Res. 2022 Jul 15;28(14):2977-2979. doi: 10.1158/1078-0432.CCR-22-1256.
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04835805