Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2022
BAMM (BRAF Autophagy and MEK Inhibition in Melanoma): A Phase I/II Trial of Dabrafenib, Trametinib, and Hydroxychloroquine in Advanced BRAFV600-mutant Melanoma.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- A comprehensive overview of the molecular features and therapeutic targets in BRAFClinical and translational medicine · 2024Pooled it
- Biomarkers and factors in small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis.Cancer medicine · 2023Pooled it
- A Phase II Open-Label Trial of Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS-Mutant Non-Small Cell Lung Cancer.The oncologist · 2023Trial
- Practical management of BRAF inhibitors in glioma: toxicity and resistance.CNS oncology · 2026Review
- Review
- Variations in Autophagy-Related GenesCancers · 2026Article
- Autophagy in Melanoma: Molecular Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- RAS/MAPK inhibition in pediatric gliomas.Neuro-oncology advances · 2026Review
- Investigating autophagy and miRNAs as therapeutic targets in leukemia.Discover oncology · 2026Review
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Crosstalk between NRP1 and autophagy in the tumor microenvironment: from molecular mechanisms to therapeutic targeting.Frontiers in immunology · 2026Review
- The crosstalk between MiRNAs and autophagy in leukemia: mechanisms and therapeutic insights.Discover oncology · 2025Review
- Inhibiting Fatty Acid Oxidation Suppresses Acquired Resistance to Standard Chemotherapy in Melanoma.International journal of molecular sciences · 2025Article
- An overview of autophagy inhibition as a potential clinical strategy in cancer therapy.Molecular pharmacology · 2025Review
- Spatio-temporal processes in autophagosome-lysosome fusion.Medical review (2021) · 2025Review
- Neobractatin and Trametinib Synergistically Induce Apoptosis and Gasdermin E-Dependent Pyroptosis in Pancreatic Cancer Cells.MedComm · 2025Article
- A comprehensive, multi-center, immunogenomic analysis of melanoma brain metastases.Acta neuropathologica communications · 2025Article
- Precision Medicine for Pediatric Glioma and NF1-Associated Tumors: The Role of Small Molecule Inhibitors.Current oncology (Toronto, Ont.) · 2025Review
- Dissecting the MAPK signaling landscape in malignant melanoma: from BRAF and NRAS mutations to precision combination therapies.Frontiers in cell and developmental biology · 2025Review
- The ubiquitination-autophagy axis in cancer therapy resistance: mechanistic insights and therapeutic opportunities.Frontiers in pharmacology · 2025Review
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Authors and funding
22 authors at 6 institutions in 1 country.
Funding
Abstract
purposeAutophagy is a resistance mechanism to BRAF/MEK inhibition in BRAFV600-mutant melanoma. Here we used hydroxychloroquine (HCQ) to inhibit autophagy in combination with dabrafenib 150 mg twice daily and trametinib 2 mg every day (D+T). PATIENTS AND
methodsWe conducted a phase I/II clinical trial in four centers of HCQ + D+T in patients with advanced BRAFV600-mutant melanoma. The primary objectives were the recommended phase II dose (RP2D) and the one-year progression-free survival (PFS) rate of >53%.
resultsThirty-four patients were evaluable for one-year PFS rate. Patient demographics were as follows: elevated lactate dehydrogenase: 47%; stage IV M1c/M1d: 52%; prior immunotherapy: 50%. In phase I, there was no dose-limiting toxicity. HCQ 600 mg orally twice daily with D+T was the RP2D. The one-year PFS rate was 48.2% [95% confidence interval (CI), 31.0%-65.5%], median PFS was 11.2 months (95% CI, 5.4-16.9 months), and response rate (RR) was 85% (95% CI, 64%-95%). The complete RR was 41% and median overall survival (OS) was 26.5 months. In a patient with elevated LDH (n = 16), the RR was 88% and median PFS and OS were 7.3 and 22 months, respectively.
conclusionsHCQ + D+T was well tolerated and produced a high RR but did not meet criteria for success for the one-year PFS rate. There was a high proportion of patients with pretreated and elevated LDH, an increasingly common demographic in patients receiving targeted therapy. In this difficult-to-treat population, the RR and PFS were encouraging. A randomized trial of D+T + HCQ or placebo in patients with BRAFV600-mutant melanoma with elevated LDH and previous immunotherapy is being conducted.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.