Clinical trial · Interventional
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 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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Melanoma | Melanoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Belvarafenib | Drug | Belvarafenib | ALIAS |
| Cobimetinib | Drug | Cobimetinib | ALIAS |
| Nivolumab | Drug | Nivolumab | ALIAS |
Design
Arms and outcomes
Arms (3)
- type
- EXPERIMENTAL
- label
- Belvarafenib Monotherapy
- description
- Twice daily (BID), continuous dosing.
- interventionNames
- Drug: Belvarafenib
- type
- EXPERIMENTAL
- label
- Belvarafenib Plus Cobimetinib
- description
- 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.
- interventionNames
- Drug: Cobimetinib
- type
- EXPERIMENTAL
- label
- Belvarafenib Plus Cobimetinib Plus Nivolumab
- description
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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 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)
References
Publications (1)
- DERIVEDMoschos 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. PMID 35587446