ArticleFrontiers in oncology2022
Phase I trial of pembrolizumab plus vemurafenib and cobimetinib in patients with metastatic melanoma.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02818023 (Dose-seeking Study of Pembrolizumab Plus Vemurafenib and Cobimetinib for Therapy of Advanced Melanoma), which is not on this map. Cited by 7 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Dose-seeking Study of Pembrolizumab Plus Vemurafenib and Cobimetinib for Therapy of Advanced Melanoma
Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
- Toxicity of immune checkpoint inhibitors and tyrosine kinase inhibitor combinations in solid tumours: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- A phase 1b study of the ERK inhibitor MK-8353 plus pembrolizumab in patients with advanced solid tumors.Investigational new drugs · 2024Article
- A phase 1 trial of the MEK inhibitor selumetinib in combination with pembrolizumab for advanced or metastatic solid tumors.Investigational new drugs · 2024Article
- Combination Atezolizumab, Cobimetinib, and Vemurafenib as a Treatment Option in BRAF V600 Mutation-Positive Melanoma: Patient Selection and Perspectives.Cancer management and research · 2024Review
- Efficacy of Pembrolizumab in Advanced Melanoma: A Narrative Review.International journal of molecular sciences · 2023Review
- The fusion of light and immunity: Advancements in photoimmunotherapy for melanoma.Photochemistry and photobiologyReview
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Preclinical and translational evidence suggest BRAF/MEK inhibitors modulate the tumor microenvironment (TME), providing rationale for combination with immunotherapy. Methods: This investigator-initiated, phase I trial evaluated pembrolizumab, vemurafenib, and cobimetinib in patients with untreated, BRAFV600E/K mutant advanced melanoma. The first 4 patients received vemurafenib with pembrolizumab, and the next 5 patients received vemurafenib and cobimetinib with pembrolizumab. Primary endpoints: safety and maximum tolerated dose of the triplet. Secondary endpoints: objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and quality of life (QoL). The trial was closed after enrollment of 9 (planned 30) patients due to dose-limiting toxicity (DLT). Study NCT02818023 was approved by the IRB, and all patients provided informed consent. Results: Patients received a median of 6 cycles of therapy. 8 of 9 experienced drug-related grade 3/4 AEs. DLTs included dermatitis (n=8), hepatitis (n=1), QTc prolongation (n=1), and arthralgias (n=1 each). QoL assessments identified a clinically significant decrease in self assessed QoL at 1 year compared to baseline (0.38 v 0.43). Median PFS was 20.7 months and median OS was 23.8 months for vemurafenib with pembrolizumab. Median PFS and OS were not reached for patients receiving triple therapy. ORR in the overall cohort was 78% (7/9). 2 patients experienced a complete response, 5 had a partial response, 1 had stable disease, and 1 had progressive disease. 4 patients had ongoing responses at data analysis. Peripheral blood flow cytometry identified significantly decreased PD1 expression on CD4+ T-cells at 3 and 9 weeks compared to baseline, not corresponding to clinical response. Conclusions: Triple therapy with vemurafenib, cobimetinib and pembrolizumab is associated with high response rates but significant adverse events, leading to early study closure.
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