On September 24, 2026 the FDA approved belzutifan (Welireg, Merck) + lenvatinib (Lenvima, Eisai) for adults with advanced renal cell carcinoma with a clear cell component following a PD-1 or PD-L1 inhibitor. In LITESPARK-011 (n=747) the combination improved median PFS to 14.6 vs 10.6 months versus cabozantinib (HR 0.74; p=0.00095; first interim analysis) and ORR to 53% vs 40%; final overall survival was not statistically significant.
Discover KOL Sentiment on LITESPARK-011 →Approval-day posts from physicians are in Physician Reactions; the reply chain under the Oncology Brothers post is below.
Posts by physicians about LITESPARK-011, newest first: ESMO 2026 week (October 17–25, 2026), the September 24, 2026 FDA approval, and earlier posts back to the ASCO GU 2026 readout and before. Each post is shown in full and verbatim and linked to the original on X.
Six more physician posts from October 25, 2026, each with the slides it shared, are in ESMO 2026 slides.
Pragmatic overview and RCC discussion with #DrNaomiHaas: LITESPARK-012 shows no benefit from intensifying 1L Pembro/Len, LITESPARK-011 supports Bel/Len after IO progression, and PE-PE explores Pembro + MDT in oligometastatic RCC. Right drugs, right setting, right patients? #RCC @myESMO @OncoAlert #ESMO26
2/2 Later-line belzutifan + lenvatinib improved PFS and response, nearly doubling time on therapy; OS benefit wasn't at the moment and is a point to discuss with patients. Inspiring to see @IMDConline founders @DrDanielHeng and @DrChoueiri in the same session as presenters!
Great presentation by @DrDanielHeng at #ESMO26 on #LITESPARK11. Congrats on simultaneous publication of the data in @Annals_Oncology! It’s a high bar to advance therapies in the 2nd line setting. I tend to still favor monotherapy for most - have had challenges with Len 20 & also want to understand more about the cardiac tox. Still, always eager to have more options to discuss with my patients! @OncoAlert
LITESPARK-011 final analysis at #ESMO26: Belzutifan + lenvatinib improved PFS (HR 0.74) but failed to significantly improve OS (HR 0.85). A promising treatment option, but PFS benefit appeared limited in the IMDC poor-risk subgroup. Patient selection remains important.
LITESPARK-011: Len-Bel improves ORR and PFS compared with Cabo in IO-pretreated mRCC, but without a statistically significant improvement in OS. Are these results good enough to establish Len-Bel as a standard therapy in this setting over Cabo monotherapy? #ESMO26
𝕏🧬 LITESPARK-011 | ESMO 2026 Better Tumor Control — But No Proven Survival Benefit! Phase III | 747 patients | Advanced ccRCC after immunotherapy 💊 Belzutifan + Lenvatinib vs Cabozantinib ✅ PFS: 14.8 vs 10.8 months (HR 0.74) ✅ ORR: 53.1% vs 40.2% ✅ DOR: 22.0 vs 11.9 months ⚠️ OS: 33.7 vs 28.6 months (HR 0.85) Despite a numerical 5.1-month advantage, OS did not meet the prespecified significance boundary (P=0.04689; required P≤0.0223). ⚠️ Grade ≥3 adverse events: 85.4% vs 83.0% 🎯 TAKE-HOME: Stronger disease control does not necessarily translate into proven longer survival. LITESPARK-011 supports the combination as a post-IO option, but OS superiority remains unproven. 📚 Reference: Heng DYC, McDermott RS, Park SH, et al. Final analysis of phase III LITESPARK-011. ESMO Congress 2026. NCT04586231. #ESMO2026 #LITESPARK011 #RenalCellCarcinoma #KidneyCancer #GUOncology #Oncology #MVOnco
New @FDA approval in advanced kidney cancer: belzutifan + lenvatinib after prior PD-1/PD-L1 therapy. Another meaningful option after IO.
FDA approves belzutifan + lenvatinib for advanced clear-cell kidney cancer (RCC) after prior immunotherapy. Compared with cabozantinib, the combination: -Delayed cancer progression (progression-free survival): 14.6 vs 10.6 months -Shrunk tumors more often (objective response rate): 53% vs 40%
JUST IN: @FDA approves the combo of Lenvatinib+HIF2 inhibitor Belzutifan in advanced clear cell renal cell carcinoma following PD1/L1 inhibitor. Results based on Litespark-011 trial led by @motzermd @DrDanielHeng @SchmidigerManu1
Today 9/24/26 new approval in 2L clear cell mRCC with some caveats #LITESPARK011 💢 4mo PFS gain, higher ORR (53% vs 40%) & DOR (23 v 12mo) 💢 OS is not yet significant 💢 how does it perform post 1L IO/IO vs IO/TKI, weight of extra toxicity & optimal sequencing still unclear
⚡️LITESPARK-011 published in @TheLancet: belzutifan + lenvatinib vs cabozantinib in advanced ccRCC after anti-PD-(L)1 therapy (n=747). Median PFS: 14.8 vs 10.7 months (HR 0.70). OS not significantly different at interim (HR 0.85). #KidneyCancer https://t.co/XI7In9Fu5v
🟪 LITESPARK-011: Belzutifan Plus Lenvatinib in Advanced RCC The phase 3 LITESPARK-011 trial evaluated belzutifan plus lenvatinib versus cabozantinib in patients with advanced clear-cell renal cell carcinoma progressing after anti-PD-1/PD-L1 therapy. The trial randomized 747 patients to belzutifan 120 mg plus lenvatinib 20 mg once daily or cabozantinib 60 mg once daily. 👉 Median PFS was 14.8 vs 10.7 months (HR 0.70; 95% CI 0.59–0.84; one-sided p<0.0001). 👉 ORR was 53% vs 40%, with median duration of response of 23.0 vs 12.3 months. 👉 Median OS was 34.9 vs 27.6 months (HR 0.85; 95% CI 0.68–1.05; one-sided p=0.061) and was not statistically significantly different at the current analysis. The investigators concluded that belzutifan plus lenvatinib might represent a potential new standard of care in this post-immunotherapy setting. @motzermd @BurottoMauricio @DrIacovelli @raymanneh @AzadOncology @UgoDeGiorgi @AndreaNecchi @FabioSchutz78 @DrDanielHeng @schmidingerRCC https://t.co/JY30LvLO5d #OncoDaily #OncoDailyGU
Just published! Litespark-011 mPFS 14.8m Lenva Belzutifan vs 10.7m Cabozantinib HR 0.7 New options for our patients💪🏻proud to be part!! @sohecsas
GU @ASCO highlights from #GU26 with @PGrivasMDPhD
✅ CREST/POTOMAC (update)
✅ EV304/KeynoteB15 (new SoC)
✅ LITESPARK-011 & 022
✅ CAPItello-281
Full 🗣️:
⭐️ On OncBrothers & @OncUpdates…
Kidney cancer trial breakdown 🎧
Brian, Tom, and @motzermd analyze the phase 3 LITESPARK-011 trial comparing belzutifan + lenvatinib vs cabozantinib—covering efficacy, safety, and implications for…
Combination therapy is emerging as a standard in refractory RCC. Combos increase tumor shrinkage endpoints. TKI provides early disease control. CRs are possible but is cure? Toxicity consideration is…
LITESPARK-011 | Phase III | #ASCOGU26 #GU26
Belzutifan + Lenvatinib vs Cabozantinib in advanced clear-cell RCC post anti–PD-(L)1
A pivotal study redefining the post-IO VEGFR-TKI landscape.
@motzermd …
More from #ASCODailyNews: Phase 3 LITESPARK-011 results support belzutifan + lenvatinib as alt to cabozantinib for pts with aRCC after disease progression on anti–PD-L1/anti–PD-1 therapy. Read the…
Thoughtful discussion by Dr. Katy Beckermann @katy_beckermann on the rationale for HIF-2α inhibitor–based combinations in LITESPARK-011 and -022, and the need to balance efficacy with quality of…
Big morning for Belzutifan🎉#ASCOGU26
#LITESPARK011 combo w/ Lenva vs Cabo in 2L+ s/p IO in mRCC (55% prior TKI)
➕ PFS, ORR, immature OS, 20 pts w/ CR
⚠️15% hypoxia, 2/3 DR TKI, 1/3 DR…
Nice slide to show take home message for Monday morning clinic after new RCC data 🙂 @ASCO #GU26 @OncoAlert https://t.co/R4hzBSrbuH
Summary of combination therapy in advanced RCC. Hard to compare phase II trials but clearly multiple options are emerging. #uromigoslive @Uromigos https://t.co/KspHdha2SJ
Daniel Y.C. Heng presented the prespecified final analysis at ESMO 2026 (abstract 3587O, October 25, 2026), published at the same time in Annals of Oncology. Median follow-up was 38.8 months (range 29.1–59.0). All figures in this block are from that analysis. (ESMO 2026 3587O / Annals of Oncology, final analysis, DCO 2 Feb 2026)
Overall survival (dual primary endpoint): not statistically significant. Median OS was 33.7 months (95% CI 29.0–46.9) with belzutifan + lenvatinib vs 28.6 months (95% CI 24.1–31.4) with cabozantinib; HR 0.85 (95% CI 0.70–1.03); one-sided P=0.04689 against a prespecified boundary of 0.0223. These are the same OS figures as in the FDA label. No overall survival benefit has been demonstrated.
Progression-free survival (dual primary endpoint) by blinded independent central review: median 14.8 vs 10.8 months; HR 0.74 (95% CI 0.62–0.88); nominal one-sided P=0.00035 (ESMO 2026 slides). PFS was statistically significant at an earlier interim analysis and was not formally re-tested at the final analysis.
Objective response rate (key secondary endpoint): 53.1% (95% CI 47.9–58.3) vs 40.2% (95% CI 35.2–45.3); nominal P=0.0002 (ESMO 2026 slides; significant at an earlier interim analysis; not formally re-tested). Median duration of response was 22.0 vs 11.9 months.
Safety: grade ≥3 treatment-emergent adverse events occurred in 85.4% vs 83.0% of patients.
In the analysis supporting the FDA approval, median PFS by blinded independent central review (RECIST v1.1) was 14.6 months (95% CI 11.1-16.6) with belzutifan + lenvatinib vs 10.6 months (95% CI 9.2-11.1) with cabozantinib; HR 0.74 (95% CI 0.61-0.89), one-sided p=0.00095 — a statistically significant improvement. (FDA approval notice / FDA label; these are the first interim analysis figures, IA1, data cut-off 26 Jun 2024 — ASCO GU 2026 LBA417)
Objective response rate was 53% (95% CI 47-58) vs 40% (95% CI 35-45); one-sided p=0.0002. (FDA label; first interim analysis, IA1)
Second interim analysis, for reference: the ASCO GU 2026 LBA417 / Lancet presentation reported median PFS 14.8 vs 10.7 months (HR 0.70; 95% CI 0.59-0.84; p=0.00007) at 29.0 months median follow-up. (ASCO GU 2026 LBA417 / Lancet; IA2, data cut-off 9 Apr 2025) The final-analysis PFS (data cut-off 2 Feb 2026) is in the ESMO 2026 block above. These come from different analyses — do not mix them.
The final analysis of overall survival was not statistically significant. Median OS was 33.7 months (95% CI 29.0-46.9) with belzutifan + lenvatinib vs 28.6 months (95% CI 24.1-31.4) with cabozantinib; HR 0.85 (95% CI 0.70-1.03). (FDA label, final analysis) One-sided P=0.04689 against a prespecified boundary of 0.0223. (ESMO 2026 3587O, final analysis, DCO 2 Feb 2026) No overall survival benefit has been demonstrated — the approval rests on PFS and ORR. An earlier interim cut reported HR 0.85 (95% CI 0.68-1.05; p=0.06075). (ASCO GU 2026 LBA417 / Lancet; IA2, data cut-off 9 Apr 2025)
The belzutifan prescribing information carries a boxed warning for embryo-fetal toxicity and warnings for anemia and hypoxia; for the belzutifan + lenvatinib combination, warnings and precautions also include cardiac dysfunction. The lenvatinib prescribing information carries warnings for hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure or impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, thyroid dysfunction, impaired wound healing, osteonecrosis of the jaw, and embryo-fetal toxicity. (FDA approval notice; full prescribing information at Drugs@FDA)
Regulatory status & clinical implications — ✅ FDA APPROVED September 24, 2026 — belzutifan (Welireg) + lenvatinib (Lenvima) for adults with advanced RCC with a clear cell component following a PD-1 or PD-L1 inhibitor. Dosage: lenvatinib 20 mg + belzutifan 120 mg once daily. (FDA approval notice) Belzutifan + lenvatinib is now an approved regimen after a PD-1 or PD-L1 inhibitor, positioned directly against single-agent cabozantinib. It is the first positive Phase 3 to combine a multi-targeted TKI with a HIF-2α inhibitor in RCC, and the first to improve PFS versus a modern TKI comparator in this post-PD-(L)1 setting. Expands role of HIF-2α inhibition beyond VEGF-TKI-refractory monotherapy.
Sponsor / Drug — Merck (with Eisai); belzutifan (HIF-2-alpha inhibitor) + lenvatinib (multikinase VEGFR TKI). (sponsor)
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated October 26, 2026.
Design — Phase 3, open-label; belzutifan (Welireg) + lenvatinib vs cabozantinib, advanced ccRCC after PD-1/PD-L1 therapy (NCT04586231); 747 patients with advanced renal cell carcinoma with a clear cell component whose disease progressed on or after a PD-1 or PD-L1 inhibitor, or within six months of completing adjuvant PD-1 therapy. (pivotal presentation)
LITESPARK-011 (NCT04586231) is a Phase 3, open-label, randomized, active-controlled trial of belzutifan (Welireg) plus lenvatinib versus cabozantinib in 747 patients with advanced renal cell carcinoma with a clear cell component after a PD-1 or PD-L1 inhibitor. See Trial Design.
Yes. On September 24, 2026 the FDA approved belzutifan (Welireg, Merck & Co., Inc.) with lenvatinib (Lenvima, Eisai Inc.) for adults with advanced renal cell carcinoma with a clear cell component following a PD-1 or PD-L1 inhibitor, based on LITESPARK-011. See FDA Approval.
Progression-free survival improved significantly versus cabozantinib (HR 0.74, 95% CI 0.61-0.89, at the first interim analysis cited in the FDA label). The benefit was maintained at the ESMO 2026 final analysis (data cut-off 2 Feb 2026; HR 0.74, 95% CI 0.62-0.88; not formally re-tested). The ASCO GU 2026 / Lancet second interim analysis reported different figures; the analyses should not be mixed. All are in At a Glance.
No. The final overall survival analysis was not statistically significant (ESMO 2026 final analysis, data cut-off 2 Feb 2026: HR 0.85, 95% CI 0.70-1.03; one-sided P=0.04689 against a boundary of 0.0223); the approval rests on progression-free survival and objective response rate. See At a Glance.
Lenvatinib 20 mg with belzutifan 120 mg once daily until disease progression or unacceptable toxicity. Belzutifan carries a boxed warning for embryo-fetal toxicity; warnings are listed in At a Glance.
Belzutifan (Welireg), a HIF-2-alpha inhibitor, is developed by Merck & Co., Inc. Lenvatinib (Lenvima), a multikinase VEGFR inhibitor, is developed by Eisai Inc. Merck Sharp & Dohme is the trial sponsor and Eisai Inc. is a listed collaborator on ClinicalTrials.gov.
