Onco-Summaries: Daily Oncology Updates at a Glance
Updated: Sep 29
24/09/2026
US FDA approves belzutifan + lenvatinib in post-IO advanced ccRCC based on PFS superiority over cabozantinib, despite no statistically significant OS benefit (Ref)
US FDA approved Merck & Co. / MSD's belzutifan (Welireg; HIF-2alpha inhibitor) in combination with Eisai & Merck & Co. / MSD's lenvatinib (Lenvima; multi-kinase inhibitor) for the treatment of adults with advanced cell carcinoma with a cell component (ccRCC) following a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.
The recommended dose is 20 mg of lenvatinib in combination with 120 mg of belzutifan once daily until disease progression or unacceptable toxicity.
Approval is supported by results from the Ph3 LITESPARK-011/NCT04586231 study evaluating belzutifan + lenvatinib vs Exelixis, Ipsen & Takeda's cabozantinib (VEGFR, MET, and AXL kinase inhibitor) in locally advanced or metastatic ccRCC which progressed on or after a PD-1 or PD-L1 inhibitor, or within six months of completing adjuvant therapy with a PD-1 inhibitor (Ref; Ref)
Parameter | Belzutifan + Lenvatinib (n=371) | Cabozantinib (n=376) | Key Result |
Patients Randomized | 371 | 376 | Total N=747 |
Median Follow-up | 29.0 months | 29.0 months | Data cutoff: Apr 9, 2025 |
Progression-Free Survival (Primary Endpoint) | 14.8 months (95% CI 11.2-16.6) | 10.7 months (95% CI 9.2-11.1) | HR 0.70 (95% CI 0.59-0.84); p<0.0001 (significantly longer) |
Overall Survival (Primary Endpoint) | 34.9 months (95% CI 27.5-NR) | 27.6 months (95% CI 24.0-31.4) | HR 0.85 (95% CI 0.68-1.05); p=0.061 (not significant) |
Objective Response Rate (ORR) | 52.6% (95% CI, 47.3-57.7) | 39.6% (95% CI, 34.6-44.8) | Statistically significant improvement |
Median Duration of Response (DOR) | 23.0 months (95% CI, 2.0-44.3+) | 12.3 months (95% CI, 1.8+-35.9+) | Nearly 2× longer response duration |
Grade ≥3 TEAEs | 84.0% | 83.0% | Comparable safety profile |
LITESPARK-011 is the first positive Phase 3 trial of a HIF-2α inhibitor combined with a multi-targeted tyrosine kinase inhibitor. Until now, evidence for treatment after ICI came from one of three sources:
Later-line data: belzutifan against everolimus in LITESPARK-005
Trials where prior ICI was optional: tivozanib against sorafenib in TIVO-3
Guideline-recommended regimens with no approval in this setting
Belzutifan + lenvatinib is the first regimen to beat an active, current TKI in patients who were required to have had ICI, improving median PFS (14.8 vs 10.7 months; HR 0.70) and ORR (52.6% vs 39.6%) over cabozantinib. This makes the doublet the strongest candidate to become NCCN's first preferred regimen after IO.
However, the final OS analysis (HR 0.85; 95% CI 0.70–1.03) did not reach statistical significance. Without a survival advantage, the combination has a weaker case for replacing the current standard of care
CSPC reports positive Phase III results for becotatug + osimertinib, demonstrating significant PFS benefit and favorable OS trend in first-Line EGFR Exon20ins NSCLC (Ref)
CSPC Pharmaceutical Group announced positive topline results from a Phase III trial evaluating becotatug (JMT101; anti-EGFR) in combination with osimertinib (EGFR-TKI) as a first-line treatment for patients with advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations.
The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival compared with platinum-based chemotherapy plus pemetrexed
The combination of becotatug and osimertinib significantly improved progression-free survival versus the chemotherapy control arm.
An encouraging trend toward overall survival benefit was also observed.
The regimen demonstrated a favorable safety profile.
The trial evaluated a chemotherapy-free approach in previously untreated patients with locally advanced or metastatic EGFR exon 20 insertion-mutated NSCLC.
Detailed study data are expected to be presented at upcoming scientific meetings
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