Clinical trial · Interventional
Phase 1 Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone
A Phase 1 Open-label Study of Safety and Tolerability of MEDI4736 in Subjects With Metastatic or Unresectable Melanoma in Combination With Dabrafenib and Trametinib or With Trametinib Alone
NCT02027961CI-TRIAL-00038686completedPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- 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)
The purpose of this study is to determine the maximum tolerated dose and characterize the safety profile of durvalumab (MEDI4736) in combination with dabrafenib and trametinib or with trametinib alone in participants with metastatic or unresectable melanoma with BRAF-mutation positive or wild-type (WT) BRAF, respectively.
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 |
|---|---|---|---|
| Dabrafenib | Drug | Dabrafenib | ALIAS |
| Durvalumab | Biological | Durvalumab | ALIAS |
| Trametinib | Drug | Trametinib | ALIAS |
Design
Arms and outcomes
Arms (4)
- type
- EXPERIMENTAL
- label
- Cohort A1: Durvalumab (3 mg/kg) + Dabrafenib +Trametinib
- description
- Participants will receive intravenous (IV) dose of 3 milligrams per kilogram (mg/kg) durvalumab every 2 weeks (Q2W) from Day 1 up to 12 months along with oral 150 mg dabrafenib capsule twice daily (BID) and oral 2 mg trametinib tablet once daily (QD) until confirmed disease progression (PD), initiation of alternate cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment. Post-durvalumab treatment period, participants who developed PD and meet the criteria for re-administration, will receive durvalumab 3 mg/kg up to an additional 12 months and continued the treatment of dabrafenib and trametinib.
- interventionNames
- Biological: Durvalumab
- Drug: Dabrafenib
- Drug: Trametinib
- type
- EXPERIMENTAL
- label
- Cohort A2: Durvalumab (10 mg/kg) + Dabrafenib +Trametinib
- description
- Participants will receive IV dose of 10 mg/kg durvalumab Q2W from Day 1 up to 12 months along with oral doses of dabrafenib 150 mg capsule BID and trametinib 2 mg tablet QD until confirmed PD, initiation of alternate cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment. Post-durvalumab treatment period, participants who developed PD and meet the criteria for re-administration, will receive durvalumab 10 mg/kg up to an additional 12 months and continued the treatment of dabrafenib and trametinib.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Adults \>= 18 years old * Histologically confirmed cutaneous melanoma that is either Stage IIIc (unresectable) or Stage IV (metastatic) and determined to be BRAF V600E or V600K mutation-positive (cohort A) or mutation-negative (cohorts B and C) * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Measurable disease by radiographic or physical examination * Adequate organ and marrow function * Willingness to provide consent for biopsies positive or BRAF WT measurable disease and adequate organ and marrow function Exclusion Criteria: * Prior treatment with a BRAF inhibitor or MEK inhibitor * Any prior Grade \>= 3 immune-related adverse event while receiving immunotherapy * Active or prior documented autoimmune disease within the past 2 years * History of or current risk for retinal vein occlusion (RVO) or central serous retinopathy (CSR) * History of or current cardiovascular risk including myocardial infarction, \>= Class II congestive heart failure, uncontrolled arrhythmias, or refractory hypertension * Active, untreated central nervous system (CNS) metastases * Women who are pregnant or lactating
References
Publications (3)
- BACKGROUNDGordon MS, Lutzky J, Lawrence D, Butler M, Ascierto PA, Hug B, et al. Phase 1 study evaluating safety and tolerability of MEDI4736, an anti-programmed cell death ligand-1 (PD-L1) antibody, in combination with dabrafenib and trametinib or trametinib alone in patients with unresectable or metastatic melanoma. Ann Oncol 2014; 25(suppl_4): iv374-iv393 (abstract 8004).
- RESULTRibas A, Butler M, Lutzky J, Lawrence DP, Robert C, Miller W, et al. Phase 1 study combining anti-PD-L1 (MEDI4736) and BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in advanced melanoma. J Clin Oncol 2015; 33 (15_suppl): (abstract 3003).
- DERIVEDRibas A, Algazi A, Ascierto PA, Butler MO, Chandra S, Gordon M, Hernandez-Aya L, Lawrence D, Lutzky J, Miller WH Jr, Campbell KM, Delafont B, Marshall S, Mueller N, Robert C. PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma. Nat Commun. 2020 Dec 7;11(1):6262. doi: 10.1038/s41467-020-19810-w. PMID 33288749