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AzTrials

MelanomaPhase 1NCT04835805

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.

A Phase 1 study testing Belvarafenib, Cobimetinib and Nivolumab in people with Melanoma, run by Genentech, Inc. at 20 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
Belvarafenib, Cobimetinib and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
20 sitesin 5 countries
Study dates
13 May 2021to 31 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • 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)

Trial locations and contacts

20 sites in 5 countries.

20 sites in 5 countries

United States8 sites

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

  • University of Iowa

    Iowa City, Iowa, 52242

  • Sarah Cannon Research Institute / Tennessee Oncology

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering

    New York, New York, 10021

  • California Pacific Medical Center Research Institute

    San Francisco, California, 94115

  • UCSF Helen Diller Family CCC

    San Francisco, California, 94158

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

Germany5 sites

  • Charité - Universitätsmedizin Berlin

    Berlin, 12203

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg, 20246

  • Klinikum Mannheim GmbH Universitätsklinikum

    Mannheim, 68167

  • Universitatsklinikum Tubingen

    Tübingen, 72076

  • Universitätsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

Australia3 sites

  • Peter MacCallum Cancer Centre-East Melbourne

    Melbourne, Victoria, 3000

  • Linear Clinical Research Ltd

    Nedlands, Western Australia, 6009

  • Calvary Mater Newcastle

    Waratah, New South Wales, 2298

Other trials in Australia

Canada2 sites

  • Ottawa Hospital Regional Cancer Centre

    Ottawa, Ontario, K1H 8M2

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

South Korea2 sites

  • Asan Medical Center - PPDS

    Seoul, 05505

  • Samsung Medical Center - PPDS

    Seoul, 06351

Other trials in South Korea

About this study

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 Nivolumab in Patients With NRAS-Mutant Advanced Melanoma Who Have Received Anti-PD-1/PD-L1 Therapy

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.

Read the detailed description

The study will evaluate three treatment regimens in three arms: a belvarafenib monotherapy arm (Belva arm); 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 nivolumab arm (Belva + Cobi + Nivo arm) in a run-in phase followed by an expansion phase.

Conditions
Melanoma
Being tested
Belvarafenib, Cobimetinib, Nivolumab
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BelvarafenibDrug

    Twice daily (BID), continuous dosing

  • CobimetinibDrug

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

  • NivolumabDrug

    Once every 4 weeks (Q4W)

Study groups in NCT04835805
Study groupRoleWhat they receive
Belvarafenib MonotherapyExperimentalTwice daily (BID), continuous dosing.
Receives: Drug: 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.
Receives: Drug: Cobimetinib
Belvarafenib Plus Cobimetinib Plus NivolumabExperimentalRecommended 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
Receives: Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Dose Limiting Toxicity (DLTs)

    Measured: 28 Days from Cycle 1, Day 1

  2. Percentage of Participants With Adverse Events

    Severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0

    Measured: From Cycle 1, Day 1 Up to 4 Years

Secondary outcomes (6)

  1. Objective response rate (ORR) according to RECIST v1.1

    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

    Measured: Up to Approximately 4 Years

  2. Progression free survival (PFS) according to RECIST v1.1

    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

    Measured: Up to Approximately 4 Years

  3. Duration of response (DOR) according to RECIST v1.1

    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

    Measured: Up to Approximately 4 Years

  4. Overall survival (OS)

    Defined as the time from the first study treatment to death from any cause

    Measured: Up to Approximately 4 Years

  5. Plasma concentration of belvarafenib at specified timepoints

    Measured: Up to 30 Days After the Final Dose of Study Drug

  6. Plasma concentration of cobimetinib at specified timepoints

    Measured: Up to 30 Days After the Final Dose of Study Drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2021
  2. Study start13 May 2021
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04835805
Sponsor's protocol ID
GO42273
Other IDs
2020-003674-41
Status last verified
Sep 2026
First submitted
6 Apr 2021
Last updated
30 Sep 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing

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.

    PubMed 35587446

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Belvarafenib, Cobimetinib and Nivolumab in people with Melanoma, run by Genentech, Inc. at 20 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States, Germany, Australia, Canada, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Dose Limiting Toxicity (DLTs) (time frame: 28 Days from Cycle 1, Day 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04835805, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026.

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