Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2026
Novel pembrolizumab-based treatments as first-line therapy in advanced clear-cell renal cell carcinoma: substudy 03A of the open-label, umbrella platform, phase I/II KEYMAKER-U03 trial.
Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04626479 (A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants With RCC), which is not on this map. Cited by 10 papers.
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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.
A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants With RCC (U03): Substudy 03A in First Line Metastatic Participants
Who cites it
10 citing papers in PubMed.
- Podcast on the Emerging Role of PD-(L)1/VEGF Bispecific Antibodies in the Evolving Advanced Renal Cell Carcinoma Treatment Landscape.Oncology and therapy · 2026Review
- Temporal trends, future projections, and burden of early-onset genitourinary cancers in Asia from 1990 to 2023: an analysis of the Global Burden of Disease Study 2023.Translational andrology and urology · 2026Article
- The clinical landscape of HIF2α inhibitors in oncology.Nature reviews. Clinical oncology · 2026Review
- The seventh kidney cancer research summit: progress in accelerating cures.The oncologist · 2026Article
- A new cuproptosis-associated lncRNA signature predicts the prognosis of clear cell renal cell carcinoma patients.Discover oncology · 2026Article
- Two-Stage Estimation of Overall Survival in the Phase 3 CheckMate 9ER Trial, Adjusting for the Impact of Subsequent Therapy.Oncology and therapy · 2026Article
- Review
- Genitourinary Oncology Highlights from the European Society for Medical Oncology Annual Meeting 2025: Advances in Renal Cell Carcinoma and Muscle-Invasive Bladder Cancer.Oncology research and treatment · 2026Review
- Deciphering the mechanistic landscape of immune checkpoint blockade in ccRCC: from molecular drivers to therapeutic responses.Frontiers in immunology · 2026Review
- Key insights from ESMO Congress 2025.Nature cancer · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
Abstract
backgroundFirst-line triplet therapy may expand clinical benefit for advanced clear-cell renal cell carcinoma (ccRCC). The phase Ib/II KEYMAKER-U03 substudy 03A (NCT04626479) investigated novel pembrolizumab (pembro)-based regimens in this setting. PATIENTS AND
methodsParticipants with advanced ccRCC and no prior systemic therapy were randomized 2 : 1 to quavonlimab (qmab)/pembro plus lenvatinib (lenva), favezelimab (fave)/pembro plus lenva, pembro plus lenva plus belzutifan (bel), and vibostolimab (vibo)/pembro plus bel or a concurrent reference treatment (pembro plus lenva). A safety lead-in of ∼10 participants occurred for all investigative treatments before randomization. Primary endpoints were objective response rate (ORR) per RECIST v1.1 by blinded independent central review in all randomized participants (excluding safety lead-in), and safety in all treated participants. Secondary endpoints included progression-free survival (PFS) and overall survival (OS).
resultsAs of 31 March 2025, 393 participants were enrolled. Median follow-up for randomized participants across the five cohorts ranged between 16 and 39 months. The ORR was 80.6% [95% confidence interval (CI) 68.6% to 89.6%] with pembro plus lenva, 71.3% (95% CI 60.0% to 80.8%) with qmab/pembro plus lenva, 62.7% (95% CI 48.1% to 75.9%) with fave/pembro plus lenva, 77.5% (95% CI 66.8% to 86.1%) with pembro plus lenva plus bel, and 42.5% (95% CI 31.5% to 54.1%) with vibo/pembro plus bel. Median PFS was 26.3 months (95% CI 15.3-39.8 months) with pembro plus lenva, 18.0 months (95% CI 11.6-34.3 months) with qmab/pembro plus lenva, 26.0 months (95% CI 8.2-31.8 months) with fave/pembro plus lenva, 31.8 months [95% CI 26.3 months-not reached (NR)] with pembro plus lenva plus bel, and 15.2 months (95% CI 12.4 months-NR) with vibo/pembro plus bel. Median OS was not reached in any arm. Grade ≥3 treatment-related adverse events occurred in 71.0% (44/62) of participants treated with pembro plus lenva, 73.3% (66/90) with qmab/pembro plus lenva, 86.9% (53/61) with fave/pembro plus lenva, 70.0% (63/90) with pembro plus lenva plus bel, and 68.9% (62/90) with vibo/pembro plus bel.
conclusionsObserved efficacy and safety of pembro plus lenva were confirmatory of prior observations for this combination. ORR was similar to reference for pembro plus lenva plus bel and qmab/pembro plus lenva, but not the other investigative arms. Further investigation of pembro plus lenva plus bel and qmab/pembro plus lenva versus pembro plus lenva is ongoing in the phase III LITESPARK-012 study.
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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.