Treatment-naive or previously treated advanced clear-cell renal cell carcinoma (ccRCC) — Merck
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Belzutifan + Cabozantinib shows promising 70% ORR in treatment-naive advanced ccRCC (LITESPARK-003). #KidneyCancer #Oncology #Cancer @OncoAlert @TheLancetOncol @DrChoueiri @kidneycan @IKCCorg…
Updated results of phase 2 LITESPARK-003 trial at #ASCOGU show durable antitumor activity after belzutifan + cabozantinib in frontline and subsequent-line treatment of patients with kidney cancer.…
Updated results from the phase 2 LITESPARK-003 study on belzutifan + cabozantinib in advanced ccRCC patients! 📊💡 Key insights into combination therapy and improved outcomes @ASCO #GU25 @DrChoueiri…
3/ LITESPARK-003 is an open-label, single-arm, phase II trial. Inclusion criteria were:
- Metastatic ccRCC
- Treatment naive (for cohort 1)
- ECOG 0–1 https://t.co/HbQwlBKAXY
Impressive response rate of 70% on the combination of Belzutifan plus Cabozantinib in Renal Cell Cancer. Update of the Ph2 LITESPARK-003 @DrChoueiri Rodolfo Perini #GU25 https://t.co/QhALNTcyWR
Dr. Scott Tykodi @UWDeptMedicine returns to the podium to share data from LITESPARK-003 combining belzutifan and cabozantinib. The combo is well tolerated. Adding belzutifan does not appear to…
An impressive 70% response rate observed with the combination of Belzutifan and Cabozantinib in renal cell cancer. Ph2 LITESPARK-003 via @DrChoueiri
https://t.co/KX7pDCYIGc
LITESPARK-003 cohort 1 demonstrated promising antitumor activity of belzutifan + cabozantinib in treatment-naive advanced ccRCC (ORR 70%, mPFS 30.3 mo, 24-mo OS 86%). The HIF-2α + multikinase inhibitor combination offers a novel 1L option but requires Phase 3 validation against established IO-based SOC (nivo+cabo, ipi+nivo, pembro+axi, pembro+lenva). Combination currently under evaluation in Phase 3 LITESPARK-011 and LITESPARK-012. Strong efficacy in IMDC poor/intermediate subgroup (59% ORR) is notable. Known class effects: anemia, hypertension, hypoxia. No new safety signals.
Median: 70 % ORR (95% CI 55-82%) (belzutifan 120mg + cabozantinib 60mg (1L, treatment-naive)). Cohort 1 (treatment-naive) ORR rate: 70% (ORR) vs. 8% (CR) vs. 62% (PR). IMDC poor/intermediate risk (n=22) ORR rate: 59% (ORR) vs. 5% (CR) vs. 55% (PR). Cohort 1 median PFS rate: 30.3% (PFS months) vs. 16.6-NR% (95% CI). Cohort 1 12-month rates rate: 69% (PFS) vs. 96% (OS). Cohort 1 24-month rates rate: 57% (PFS) vs. 86% (OS). Phase 2 open-label, single-arm, multi-center study. Cohort 1: 50 treatment-naive evaluable patients (median age 64, 80% male, 96% White, 66% ECOG PS 0, 56% favorable IMDC risk, 80% prior nephrectomy). Intervention: belzutifan 120mg + cabozantinib 60mg orally daily. Primary endpoint ORR 70% (95% CI 55-82%) with 8% CR + 62% PR. IMDC poor/intermediate (n=22): ORR 59% (95% CI 36-79%) with 5% CR + 55% PR. Median PFS 30.3 months (95% CI 16.6-NR). Median OS not reached (95% CI NR-NR). 12-mo PFS 69%, 24-mo PFS 57%. 12-mo OS 96%, 24-mo OS 86%. Choueiri et al., Lancet Oncol 2025;26(1):64-73.
Median OS not reached in cohort 1 (treatment-naive). 12-month OS 96% (95% CI 84.2-98.9%); 24-month OS 86% (95% CI 68.2-94.0%). 5 (10%) deaths at data cutoff. Cohort 2 (previously treated with prior IO, N=52) previously reported separately. Strong signal supports further investigation; combination under evaluation in Phase 3 trials.
Key AEs: Grade 1/2: anemia (76%), diarrhea (74%), fatigue (58%), ALT increase (52%), nausea (52%), Grade 3/4: hypertension (12%), anemia (10%), fatigue (8%), hypoxia (6%), palmar-plantar erythrodysesthesia (6%). All 50 patients had at least 1 any-grade AE, 60% experienced ≥1 Grade ≥3 AE. Serious treatment-related AEs 14%. NO TREATMENT-RELATED DEATHS. Belzutifan dose reductions 28%, interruptions 48%. Treatment-emergent hypoxia (6% G3/4) is a known belzutifan class effect (HIF-2α inhibition).
🔄 Phase 2 signal supports Phase 3 development in 1L ccRCC. LITESPARK-003 cohort 1 demonstrated promising antitumor activity of belzutifan + cabozantinib in treatment-naive advanced ccRCC (ORR 70%, mPFS 30.3 mo, 24-mo OS 86%). The HIF-2α + multikinase inhibitor combination offers a novel 1L option but requires Phase 3 validation against established IO-based SOC (nivo+cabo, ipi+nivo, pembro+axi, pembro+lenva). Combination currently under evaluation in Phase 3 LITESPARK-011 and LITESPARK-012. Strong efficacy in IMDC poor/intermediate subgroup (59% ORR) is notable. Known class effects: anemia, hypertension, hypoxia. No new safety signals.
