🔬🧬 Oncology Updates: Tagrisso survival boost, J&J combo win and More
From dual-target EGFR strategies and FDA designations in KRAS G12C to China’s approval in HER2-mutant NSCLC, next-gen HER2 diagnostics, pediatric CNS momentum, and biliary/GBM advances—this roundup spans lung, brain, breast, biliary, and cervical cancers driving precision oncology forward.
In Today’s Newsletter
🧬 Tagrisso + chemo hits ~4-year median OS in 1L EGFRm NSCLC (FLAURA2) [1] [07 Sep 2025]
Context: Phase III FLAURA2; 557 pts; OS data cut-off 12 Jun 2025; chemo drove higher ≥G3 AEs; safety manageable.
Key point: Median OS 47.5 vs 37.6 months; HR 0.77 (95% CI 0.61–0.96; p=0.0202); consistent across subgroups.
Implication: May influence prescriber choice and payer reviews pending full data.
📄 NEJM: Amivantamab + lazertinib improves OS vs osimertinib in 1L EGFRm NSCLC (MARIPOSA) [2] [EU • 07 Sep 2025]
Context: Phase 3; median follow-up 37.8 mo; additional benefits in time to subsequent therapy and PFS2.
Key point: OS HR 0.75 (95% CI 0.61–0.92; P=0.005) vs osimertinib; median OS not reached; projected >4 years (per source).
Implication: May influence prescriber choice and payer reviews pending full data.
🚀 FDA grants BTD to olomorasib + pembrolizumab in 1L KRAS G12C, PD-L1 ≥50% NSCLC [3] [US • 04 Sep 2025]
Context: Based on Phase 1/2 LOXO-RAS-20001 and Phase 3 SUNRAY-01 dose-optimization; WCLC 2025 updates planned.
Key point: Breakthrough Therapy designation for unresectable/metastatic KRAS G12C NSCLC with PD-L1 ≥50% in combination with pembrolizumab.
Implication: May influence prescriber choice and payer reviews pending full data.
✅ China approves HERNEXEOS (zongertinib) for previously treated HER2-mutant NSCLC [4] [China • 01 Sep 2025]
Context: Conditional NMPA approval; Phase Ib Beamion-LUNG-1 ORR 71% (N=75); mPFS 12.4 mo; mDoR 14.1 mo; manageable safety.
Key point: First oral targeted therapy option for this segment in China; also holds Breakthrough Therapy Designation for 1L setting.
Implication: Introduces competition that may affect pricing and formulary access.
🧪 CE-IVDR expansion: Roche HER2 (4B5) CDx adds HER2-ultralow breast & HER2+ BTC use [5] [EU • 05 Sep 2025]
Context: VENTANA HER2 (4B5) RxDx assay; enables ENHERTU in HER2-ultralow HR+ mBC; identifies BTC IHC 3+ for ZIIHERA (zanidatamab-hrii).
Key point: First CDx approved for HER2-ultralow mBC; first CDx to identify HER2-positive BTC eligible for zanidatamab-hrii.
Implication: May expand screening, initiation, and follow-up at scale.
🇭🇰 Hong Kong approves TIVDAK (tisotumab vedotin) for recurrent/metastatic cervical cancer [6] [Hong Kong • 01 Sep 2025]
Context: Post-chemotherapy setting; ADC against tissue factor; NMPA BLA accepted Mar 2025.
Key point: First ADC in cervical cancer available in Hong Kong per source; strengthens Zai Lab’s women’s health franchise.
Implication: Introduces competition that may affect pricing and formulary access.
🧒 Lantern completes FDA Type C meeting on pediatric CNS trial for LP-184/STAR-001 [7] [US • 03 Sep 2025]
Context: Planned pediatric CNS study incl. ATRT parallel cohort; potential spironolactone combo; Rare Pediatric Disease and Orphan designations.
Key point: FDA feedback clarified design/combination path; IND amendment planned; trial start targeted Q1 2026 (per source).
Implication: Signals pipeline investment and modality expansion.
🧠 BPGbio completes enrollment in single-arm Phase 2b GBM study of BPM31510 + vitamin K1 [8] [US • 04 Sep 2025]
https://firstwordpharma.com/story/5994919
Context: Newly diagnosed GBM; 50 pts across U.S. sites; therapy delivered before SOC RT/TMZ; primary endpoint PFS at 6 months.
Key point: Enrollment complete; trial-in-progress at ESMO/SNO 2025; topline expected 1H 2026 (per source).
Implication: May influence prescriber choice and payer reviews pending full data.
💉 Glenmark starts ex-China Phase 3 of subcutaneous PD-L1 envafolimab in resectable Stage III NSCLC [9] [India • 05 Sep 2025]
https://firstwordpharma.com/story/5995158
Context: DCGI NOC to enroll in India; CTAs in Russia, Brazil, Mexico; Stage IIIA/IIIB (N2) perioperative setting; parallel China P3 active.
Key point: Multi-country pivotal program for SC PD-L1 to improve access/convenience in Stage III NSCLC.
Implication: May influence prescriber choice and payer reviews pending full data.
🌐 Akeso completes enrollment: Phase III ivonescimab vs durvalumab combo in 1L biliary tract cancer [10] [China • 02 Sep 2025]
Context: AK112-309/HARMONi-GI1; registrational, randomized; conducted in China; ivonescimab targets PD-1 and VEGF.
Key point: Enrollment complete; head-to-head vs durvalumab + chemotherapy in 1L BTC.
Implication: May influence prescriber choice and payer reviews pending full data.
Why it matters
EGFR landscape is shifting, with dual-targeted regimens [2] and chemo backbones [1] both showing survival gains over osimertinib alone.
KRAS G12C moves earlier: BTD for olomorasib + IO [3] signals potential first-line combination competition.
Regional access accelerates: China’s zongertinib approval [4] and Hong Kong’s TIVDAK OK [6] broaden targeted and ADC options.
Diagnostics unlock patients: CE-IVDR expansions for HER2 testing [5] enable therapy for HER2-ultralow mBC and HER2-positive BTC.
FAQ
What’s new about Tagrisso + chemo in FLAURA2?
AstraZeneca reports median OS ~47.5 months vs 37.6 with monotherapy (HR 0.77; p=0.0202) in 1L EGFRm NSCLC, with manageable safety consistent with known profiles [1].
How strong is the amivantamab + lazertinib OS signal?
NEJM-published MARIPOSA shows OS HR 0.75 vs osimertinib (P=0.005); median OS not reached and projected to exceed four years per the company release [2].
Which patients are covered by Lilly’s BTD for olomorasib?
Unresectable/metastatic NSCLC with KRAS G12C and PD-L1 ≥50%, in combination with pembrolizumab as first-line therapy; based on LOXO-RAS-20001 and SUNRAY-01 data [3].
Who can receive HERNEXEOS (zongertinib) in China now?
Adults with unresectable, locally advanced/metastatic NSCLC harboring activating HER2 mutations who have had ≥1 prior systemic therapy; approval supported by ORR 71% in Beamion-LUNG-1 [4].
How do Roche’s HER2 (4B5) label expansions change practice?
They enable identification of HER2-ultralow HR+ mBC for ENHERTU and HER2-positive BTC (IHC 3+) for zanidatamab-hrii (ZIIHERA), potentially expanding eligible populations [5].
What differentiates envafolimab and ivonescimab trials?
Envafolimab is a subcutaneous PD-L1 in perioperative Stage III NSCLC (ex-China Phase 3 initiation) [9]; ivonescimab is a PD-1/VEGF bispecific completing 1L BTC Phase 3 enrollment vs durvalumab + chemo in China [10].
Entities / Keywords
AstraZeneca; Tagrisso (osimertinib) • Johnson & Johnson / Janssen; Rybrevant (amivantamab) + lazertinib (LAZCLUZE/LACLaza) • Eli Lilly; olomorasib (LY3537982); KRAS G12C; pembrolizumab (Keytruda) • Boehringer Ingelheim; HERNEXEOS (zongertinib); HER2-mutant NSCLC; Beamion-LUNG-1 • Roche; VENTANA HER2 (4B5) RxDx; ENHERTU (trastuzumab deruxtecan); ZIIHERA (zanidatamab-hrii) • Zai Lab; TIVDAK (tisotumab vedotin) • Lantern Pharma / Starlight Therapeutics; LP-184/STAR-001; spironolactone; ATRT • BPGbio; BPM31510 (ubidecarenone/CoQ10 nanoliposome) • Glenmark; envafolimab (subcutaneous PD-L1; Alphamab/3D Medicines) • Akeso; ivonescimab (PD-1/VEGF; AK112); durvalumab.
References
https://firstwordpharma.com/story/5994919