Clinical trial · Interventional
A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma
A Randomized, Double-blind, Placebo-controlled, Phase III Study Comparing the Combination of PDR001, Dabrafenib and Trametinib Versus Placebo, Dabrafenib and Trametinib in Previously Untreated Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
NCT02967692CI-TRIAL-00095383COMBI-iterminatedPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): Sponsor decision
Summary
Brief summary (as posted)
The purpose of this study was to evaluate safety and efficacy of the combination of an anti-PD-1 antibody (PDR001), a BRAF inhibitor (dabrafenib) and a MEK inhibitor (trametinib) in patients with BRAF V600 mutant, unresectable and metastatic melanoma.
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 (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Dabrafenib | Drug | Dabrafenib | ALIAS |
| Placebo | Other | — | UNRESOLVED |
| Spartalizumab | Biological | — | UNRESOLVED |
| Trametinib | Drug | Trametinib | ALIAS |
Design
Arms and outcomes
Arms (4)
- type
- EXPERIMENTAL
- label
- Part 1: Safety run-in Cohort
- description
- In Part 1, participants are treated at different dose levels to determine the recommended Phase 3 regimen of spartalizumab in combination with dabrafenib and trametinib. The starting dose of spartalizumab is 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).
- interventionNames
- Biological: Spartalizumab
- Drug: Dabrafenib
- Drug: Trametinib
- type
- EXPERIMENTAL
- label
- Part 2: Biomarker cohort
- description
- In Part 2, participants are treated with spartalizumab 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).
- interventionNames
- Biological: Spartalizumab
- Drug: Dabrafenib
- Drug: Trametinib
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 100 Years
Show eligibility criteria text
Inclusion criteria Part 1: Safety run-in * Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation * Aspartate transaminase (AST) \< 2.5× ULN and Alanine transaminase (ALT) \< 2.5× ULN * Measurable disease according to RECIST 1.1 * ECOG performance status ≤ 1 Part 2: Biomarker cohort * Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation * At least two cutaneous or subcutaneous or nodal lesions for tumor sample collection * Measurable disease according to RECIST 1.1 * ECOG performance status ≤ 2 Part 3: Double-blind, randomized, placebo-controlled part * Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation * ECOG performance status ≤ 2 * Measurable disease according to RECIST 1.1 Exclusion Criteria: Part 1: Safety run-in * Subjects with uveal or mucosal melanoma * Any history of CNS metastases * Prior systemic anti-cancer treatment for unresectable or metastatic melanoma * Neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to enrollmen * Radiation therapy within 4 weeks prior to start of study treatment * Active autoimmune disease, and/or history of autoimmune disease(s) that required treatment Parts 2 \& 3: Biomarker cohort \& double-blind, randomized, placebo-controlled part * Subjects with uveal or mucosal melanoma * Prior systemic anti-cancer treatment for unresectable or metastatic melanoma * Neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to enrollment * Radiation therapy within 4 weeks prior to start of study treatment * Clinically active cerebral melanoma metastasis. * Active autoimmune disease, and/or history of autoimmune disease(s) that required treatment Other protocol-defined Inclusion/Exclusion may apply.
References
Publications (4)
- DERIVEDRibas A, Robert C, Schadendorf D, Long GV, Tawbi H, Flaherty K, Ascierto PA, Nathan P, Rutkowski P, Leonov OV, Lorigan P, Prey S, Saponara M, Arance A, Gaudy-Marqueste C, Stroyakovskiy D, Lebbe C, Maio M, Del Vecchio M, Boghikian PS, Gutzmer R, Depenni R, Miskic M, Russo M, Dummer R. COMBI-I: Long-Term Overall Survival With Spartalizumab Plus Dabrafenib and Trametinib in BRAF V600-Mutant Advanced Melanoma. J Clin Oncol. 2026 Aug 12:JCO2600528. doi: 10.1200/JCO-26-00528. Online ahead of print. PMID 42585631
- DERIVEDTawbi HA, Robert C, Brase JC, Gusenleitner D, Gasal E, Garrett J, Savchenko A, Gorgun G, Flaherty KT, Ribas A, Dummer R, Schadendorf D, Long GV, Nathan PD, Ascierto PA. Spartalizumab or placebo in combination with dabrafenib and trametinib in patients with BRAF V600-mutant melanoma: exploratory biomarker analyses from a randomized phase 3 trial (COMBI-i). J Immunother Cancer. 2022 Jun;10(6):e004226. doi: 10.1136/jitc-2021-004226. PMID 35728875
- DERIVEDDummer R, Long GV, Robert C, Tawbi HA, Flaherty KT, Ascierto PA, Nathan PD, Rutkowski P, Leonov O, Dutriaux C, Mandala M, Lorigan P, Ferrucci PF, Grob JJ, Meyer N, Gogas H, Stroyakovskiy D, Arance A, Brase JC, Green S, Haas T, Masood A, Gasal E, Ribas A, Schadendorf D. Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600-Mutant Unresectable or Metastatic Melanoma. J Clin Oncol. 2022 May 1;40(13):1428-1438. doi: 10.1200/JCO.21.01601. Epub 2022 Jan 14. PMID 35030011
- DERIVEDDummer R, Lebbe C, Atkinson V, Mandala M, Nathan PD, Arance A, Richtig E, Yamazaki N, Robert C, Schadendorf D, Tawbi HA, Ascierto PA, Ribas A, Flaherty KT, Pakhle N, Campbell CD, Gusenleitner D, Masood A, Brase JC, Gasal E, Long GV. Combined PD-1, BRAF and MEK inhibition in advanced BRAF-mutant melanoma: safety run-in and biomarker cohorts of COMBI-i. Nat Med. 2020 Oct;26(10):1557-1563. doi: 10.1038/s41591-020-1082-2. Epub 2020 Oct 5. PMID 33020648