Welireg (belzutifan) / Merck (MSD) - LARVOL DELTA

Adjuvant pembrolizumab plus belzutifan versus placebo in clear cell renal cell carcinoma: a reconstructed survival data analysis of the KEYNOTE-564 and the LITESPARK-022 trials. (PubMed, ESMO Open) - "Adjuvant pembrolizumab plus belzutifan showed a substantial DFS benefit compared with placebo. In a context where factors beyond efficacy demand robust evidence of clinical benefit, these findings reinforce the value of combined immune and hypoxia-inducible factor 2α inhibition."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • PD-L1

Real-world effectiveness and safety of belzutifan in metastatic clear-cell renal cell carcinoma: a multicentre retrospective analysis in Germany (ESMO 2026) - No abstract available

Metastases • Real-world • Real-world effectiveness • Real-world evidence • Retrospective data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Real-World Toxicity Signature of Belzutifan in Advanced Renal Cell Carcinoma: Insights From the FAERS Database (ESMO 2026) - No abstract available

Clinical • Metastases • Real-world • Real-world evidence • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Gastrointestinal and Renal Adverse Events following Kidney SBRT for Renal Cell Carcinoma: Impact of Recent Systemic Therapy Use (ASTRO 2026) - "Recent systemic therapy was defined as RCC-directed agent within 6 months pre- or 12 months post-SBRT, classified as multitarget tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), or other (everolimus, belzutifan, bevacizumab)...TKIs included cabozantinib (n=11), axitinib (n=9), lenvatinib (n=8), and tivozanib (n=1)... BP rates were higher among kidney SBRT patients treated with recent combination TKI+ICI therapy. Given the retrospective design and limited sample size, results should be interpreted cautiously."

Adverse events • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

LITESPARK-034: phase 3 study of belzutifan plus zanzalintinib versus belzutifan in participants with advanced renal cell carcinoma (RCC) during or after anti–PD-(L)1 therapy and VEGF-TKI (ESMO 2026) - No abstract available

Metastases • P3 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Belzutifan Beyond Clinical Trials: Multicenter Real World (RW) Outcomes in Metastatic Renal Cell Carcinoma (RCC) (ESMO 2026) - No abstract available

Clinical • Metastases • Real-world • Real-world evidence • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Adjuvant pembrolizumab plus belzutifan versus placebo in clear cell renal cell carcinoma: a reconstructed survival data analysis of the KEYNOTE-564 and the LITESPARK-022 trials (ESMO 2026) - No abstract available

Clinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

LITESPARK-015: Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015) (clinicaltrials.gov) - P2 | N=355 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Dec 2029 ➔ Nov 2032 | Trial primary completion date: Dec 2029 ➔ Nov 2032

Monotherapy • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Gastrointestinal Neuroendocrine Tumor • Gastrointestinal Stromal Tumor • Neuroendocrine Tumor • Oncology • Sarcoma • Solid Tumor • Von Hippel-Lindau Syndrome

Relationship between health-related quality of life (HRQoL) and efficacy in LITESPARK-011: Belzutifan (belz) + lenvatinib (len) versus cabozantinib (cabo) in advanced clear cell renal cell carcinoma (ccRCC) after anti–PD-(L)1 therapy (ESMO 2026) - No abstract available

Clinical • HEOR • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Final analysis of the phase 3 LITESPARK-011 study: belzutifan (bel) plus lenvatinib (len) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti–PD-(L)1 therapy (ESMO 2026) - No abstract available

Metastases • P3 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

First-line pembrolizumab + lenvatinib + belzutifan or MK-1308A + lenvatinib in advanced RCC: randomized open-label phase 3 LITESPARK-012 study (ESMO 2026) - No abstract available

Clinical • Metastases • P3 data • Oncology • Renal Cell Carcinoma

Renal Cell Carcinomaâs Rare Colonic Twist: A Diagnostic Challenge (ACG 2026) - "Case Description/ A 71-year-old female with a history of clear cell RCC with prior peritoneal metastasis (status-post right radical nephrectomy) currently on belzutifan presented with hematochezia...Figure: Figure 2. Histopathology of biopsy specimen obtained from the colonic mass consistent with clear cell renal cell carcinoma."

Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Hepatocellular Cancer • Hepatology • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Belzutifan Plus Lenvatinib Versus Cabozantinib in Post–PD-(L)1 Renal Cell Carcinoma: Health-Related Quality-of-Life Outcomes in the Phase 3 LITESPARK-011 Study (KCRS 2026) - P3 | "This abstract was accepted and previously presented at the 2026 ASCO Annual Meeting. Keywords Belzutifan, Lenvatinib, Renal Cell Carcinoma, Quality of Life, Patient Reported Outcomes."

Clinical • HEOR • P3 data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Therapeutic Optimization, Biomarker Development, and Emerging Strategies in Kidney Cancer. (PubMed, Kidney Cancer J) - "LITESPARK-022 demonstrated superiority of belzutifan plus pembrolizumab over pembrolizumab alone in the adjuvant high-risk clear cell RCC (ccRCC) setting - a first for any combination in adjuvant solid tumor oncology. LITESPARK-011 established belzutifan plus lenvatinib as a superior post-immunotherapy option over cabozantinib in advanced ccRCC, the first phase III superiority result in this context...Biomarker development and emerging strategies - including radiation as an immune sensitizer and novel mechanistic combinations - pointed toward the field's next frontiers. GU26 signaled a new era of therapeutic sophistication in RCC, with patient selection, biomarker validation, and inclusive trial design as defining priorities ahead."

Biomarker • IO biomarker • Journal • Genito-urinary Cancer • Kidney Cancer • Non Clear Cell Renal Cell Carcinoma • Oncology • Renal Cell Carcinoma • Solid Tumor • EPAS1

FDA approves belzutifan in combination with lenvatinib for advanced renal cell carcinoma with a clear cell component (FDA) - "Efficacy was evaluated in LITESPARK-011 (NCT04586231), an open-label, randomized, active-controlled trial in 747 patients with advanced ccRCC...The recommended dosage is 20 mg of lenvatinib in combination with 120 mg of belzutifan once daily until disease progression or unacceptable toxicity."

FDA approval • Clear Cell Renal Cell Carcinoma

KEYMAKER-U03 Substudy 03B: Pembrolizumab (pembro) and targeted therapy combinations for advanced clear cell renal cell carcinoma (ccRCC). (ASCO-GU 2025) - P1/2 | "Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Clinical Trial Registration Number: NCT04626518 Background: The phase 1/2 KEYMAKER-U03 Substudy 03B (NCT04626518) is being conducted to evaluate combination treatments for previously treated advanced ccRCC. Lenvatinib + belzutifan (arm B5) exhibited durable antitumor activity and a safety profile consistent with the individual profiles of the drugs. Results from Substudy-03B support further investigation of lenvatinib + belzutifan combination for pts with advanced RCC, as in LITESPARK-011."

Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • EPAS1

Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043) (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jan 2034 ➔ Apr 2034 | Trial primary completion date: Jan 2034 ➔ Apr 2034

Trial completion date • Trial primary completion date • Oncology • Von Hippel-Lindau Syndrome

Belzutifan (bel) plus lenvatinib (lenva) versus cabozantinib (cabo) for advanced renal cell carcinoma (RCC) after anti–PD-(L)1 therapy: Open-label phase 3 LITESPARK-011 study. (ASCO-GU 2026) - P3 | "Bel + lenva demonstrated superior PFS and ORR vs cabo in pts with advanced ccRCC following anti–PD-(L)1 therapy. OS favored bel + lenva but did not reach statistical significance and will be tested further at final analysis. The safety profile of bel + lenva was consistent with the profiles of the individual drugs."

Clinical • Late-breaking abstract • Metastases • P3 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • EPAS1

Belzutifan plus lenvatinib for patients (pts) with advanced clear cell renal cell carcinoma (ccRCC) after progression on a PD-1/L1 and VEGF inhibitor: Preliminary results of arm B5 of the phase 1/2 KEYMAKER-U03B study. (ASCO 2023) - P1b/2 | "Preliminary data from the belzutifan + lenvatinib combination exhibited promising antitumor activity in pts with ccRCC that progressed on PD-1/L1 inhibitors and VEGF-TKIs. Safety findings were consistent with individual profiles of each agent. The combination is being further evaluated in the phase 3 LITESPARK-011 study."

Clinical • Metastases • P1/2 data • Anemia • Cardiovascular • Clear Cell Renal Cell Carcinoma • Fatigue • Genito-urinary Cancer • Hematological Disorders • Hypertension • Oncology • Pulmonary Disease • Renal Cell Carcinoma • Solid Tumor • EPAS1

Update on combined immunotherapy for the treatment of advanced renal cell carcinoma. (PubMed, Hum Vaccin Immunother) - P2 | "A recently conducted trial (COSMIC-313) showed superior efficacy with a triplet combination of cabozantinib, nivolumab, and ipilimumab when compared to a placebo, nivolumab, and ipilimumab but at the cost of additional toxicity. Many other combination treatments, such as pembrolizumab plus lenvatinib plus belzutifan (NCT04976634), are being investigated, possibly leading to more options in the first-line setting in the future."

Journal • Metastases • Review • Genito-urinary Cancer • Immune Modulation • Oncology • Renal Cell Carcinoma • Solid Tumor

First-line pembrolizumab-based regimens for advanced clear cell renal cell carcinoma: KEYMAKER-U03 substudy 03A (ESMO 2025) - P1/2 | "Methods Adults with advanced ccRCC and no prior systemic therapy were randomized 2:1 to open investigational arms or the reference (ref): coformulated quavonlimab (qmab; anti-CTLA-4)/pembro + lenvatinib (lenva; VEGFR-TKI); coformulated favezelimab (fave; anti-LAG-3)/pembro + lenva; pembro + lenva + belzutifan (bel; HIF-2α inhibitor); coformulated vibostolimab (vibo; anti-TIGIT)/pembro + bel; ref, pembro + lenva. Other regimens did not show improved ORR and PFS compared with pembrolizumab + lenvatinib, yet the duration of follow-up was insufficient to detect long-term contributions to OS. Safety profiles were consistent with the profiles of the individual drugs in each regimen."

Clinical • Late-breaking abstract • Metastases • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • EPAS1 • TIGIT

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. (PubMed, Ann Oncol) - P1/2 | "Observed 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 3 LITESPARK-012 study."

Journal • P1/2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial. (PubMed, Lancet) - P3 | "Belzutifan-lenvatinib represents a novel and efficacious treatment option. Although overall survival was not significantly different between the groups, belzutifan-lenvatinib might be a new standard of care for patients with advanced clear-cell renal cell carcinoma with disease progression after previous anti-PD-1 or anti-PD-L1 therapy. The safety profile of belzutifan-lenvatinib was consistent with those of the individual drugs."

Journal • P3 data • Cardiovascular • Genito-urinary Cancer • Hypertension • Oncology • Renal Cell Carcinoma • Solid Tumor

LITESPARK-013: A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013) (clinicaltrials.gov) - P2 | N=154 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CTLA4

NEBULA: Neoadjuvant Belzutifan Plus Pembrolizumab in High-Risk, Locally Advanced Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Peter MacCallum Cancer Centre, Australia

New P2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor