Trial reportMolecular cancer research : MCR2021
High Response Rate and Durability Driven by HLA Genetic Diversity in Patients with Kidney Cancer Treated with Lenvatinib and Pembrolizumab.
Trial report in Molecular cancer research : MCR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- FGFR as a Predictive Marker for Targeted Therapy in Gastrointestinal Malignancies: A Systematic Review.Journal of gastrointestinal cancer · 2025Pooled it
- Genomic diversity in functionally relevant genes modifies neurodevelopmental versus neoplastic risks in individuals with germline PTEN variants.NPJ genomic medicine · 2025Article
- Overview on biomarkers for immune oncology drugs.Exploration of targeted anti-tumor therapy · 2025Review
- HLA gene polymorphism is a modifier of age-related breast cancer penetrance in carriers of BRCA1 pathogenic alleles.Breast cancer research and treatment · 2025Article
- Combination Targeted Therapy with Pembrolizumab and Lenvatinib in Progressive, Radioiodine-Refractory Differentiated Thyroid Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- A spatial architecture-embedding HLA signature to predict clinical response to immunotherapy in renal cell carcinoma.Nature medicine · 2024Article
- Current Landscape of Cancer Immunotherapy: Harnessing the Immune Arsenal to Overcome Immune Evasion.Biology · 2024Review
- Pan-cancer evaluation of regulated cell death to predict overall survival and immune checkpoint inhibitor response.NPJ precision oncology · 2024Article
- The 5th Kidney Cancer Research Summit: Research Accelerating Cures for Renal Cell Carcinoma in 2023.The oncologist · 2024Article
- Evaluation of potential biomarkers for lenvatinib plus pembrolizumab among patients with advanced endometrial cancer: results from Study 111/KEYNOTE-146.Journal for immunotherapy of cancer · 2024Article
- The Evolving Landscape of Biomarkers for Immune Checkpoint Blockade in Genitourinary Cancers.Biomarker insights · 2024Review
- Antigen presentation in cancer - mechanisms and clinical implications for immunotherapy.Nature reviews. Clinical oncology · 2023Review
- Novel Genetic Subtypes of Urothelial Carcinoma With Differential Outcomes on Immune Checkpoint Blockade.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Immunodiagnosis - the promise of personalized immunotherapy.Frontiers in immunology · 2023Review
- Heterozygote advantage at HLA class I and II loci and reduced risk of colorectal cancer.Frontiers in immunology · 2023Article
- Impact of germline HLA genotypes on clinical outcomes in patients with urothelial cancer treated with pembrolizumab.Cancer science · 2022Article
- Facts and Hopes for Immunotherapy in Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Solving the puzzle of what makes immunotherapies work.Trends in cancer · 2022Review
- Next-generation sequencing: unraveling genetic mechanisms that shape cancer immunotherapy efficacy.The Journal of clinical investigation · 2022Review
- Novel emerging biomarkers to immunotherapy in kidney cancer.Therapeutic advances in medical oncology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 4 institutions in 2 countries.
Funding
Abstract
Immune checkpoint blockade (ICB) therapy has substantially improved the outcomes of patients with many types of cancers, including renal cell carcinoma (RCC). Initially studied as monotherapy, immunotherapy-based combination regimens have improved the clinical benefit achieved by ICB monotherapy and have revolutionized RCC treatment. While biomarkers like PD-L1 and tumor mutational burden (TMB) are FDA approved as biomarkers for ICB monotherapy, there are no known biomarkers for combination immunotherapies. Here, we describe the clinical outcomes and genomic determinants of response from a phase Ib/II clinical trial on patients with advanced RCC evaluating the efficacy of lenvatinib, a multi-kinase inhibitor mainly targeting VEGFR and FGFR plus pembrolizumab, an anti-PD1 immunotherapy. Concurrent treatment with lenvatinib and pembrolizumab resulted in an objective response rate of 79% (19/24) and tumor shrinkage in 96% (23/24) of patients. While tumor mutational burden (TMB) did not predict for clinical benefit, germline HLA-I diversity strongly impacted treatment efficacy. Specifically, HLA-I evolutionary divergence (HED), which measures the breadth of a patient's immunopeptidome, was associated with both improved clinical benefit and durability of response. Our results identify lenvatinib plus pembrolizumab as a highly active treatment strategy in RCC and reveal HLA-I diversity as a critical determinant of efficacy for this combination. HED also predicted better survival in a separate cohort of patients with RCC following therapy with anti-PD-1-based combination therapy. IMPLICATIONS: These findings have substantial implications for RCC therapy and for understanding immunogenetic mechanisms of efficacy and warrants further investigation.
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Registered trials
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.