Kunal Jobanputra/LinkedIn
Apr 30, 2025, 09:45
Kunal Jobanputra: Zongertinib in HER2-mutant NSCLC
Kunal Jobanputra, Consultant Medical Oncologist at Saifee Hospital, shared a post on X:
“Zongertinib in HER2-mutant NSCLC
Zongertinib (BI 1810631):
Oral, irreversible HER2-selective TKI designed to minimize EGFR-related toxicity.Mechanism of Action:
Irreversibly inhibits HER2, blocking oncogenic signaling in HER2-mutant NSCLC.Differentiation:
Unlike pan-HER TKIs (pyrotinib, poziotinib), spares EGFR, reducing diarrhea and rash (17-26% grade ≥3 diarrhea, 47-49% grade ≥3 rash with poziotinib).
Reduced ILD : No ILD due to oral TKI mechanism, avoiding antibody-drug conjugate (ADC) payload-related lung toxicity seen in ADCs like trastuzumab deruxtecan (13-26% ILD).
Efficacy in Beamion LUNG-1 Trial
Cohort 1: TKD Mutations (120 mg)
• Response : 71% ORR , 14.1m DoR , 12.4m PFS .
• Major Mutations : A775_G776insYVMA (57%), P780_Y781insGSP (11%), other TKD mutations (32%).
• Grade ≥3 AEs : 17% (8% ALT increase, 5% AST increase, 1% diarrhea). No ILD .Cohort 3: Non-TKD Mutations
• Response : 30% ORR , DoR/PFS immature.
• Grade ≥3 AEs : 25% Active across diverse mutations.Cohort 5: Prior ADC Treatment (120 mg)
• Response : 48% ORR , 5.3m DoR, 6.8m PFS.
• Grade ≥3 AEs : 3% (minimal details). Effective post-trastuzumab deruxtecan (41% ORR).Safety Profile
• Common AEs : 56% diarrhea (1% grade 3) , 33% rash (0% grade 3) .
• Safety Advantage : No ILD risk, unlike ADCs (trastuzumab deruxtecan: 13-26% ILD; rezetecan: 7% ILD). Low discontinuation rate (3%).
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May 31, 2024
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OncoThon 2024, Online
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Global Summit on War & Cancer 2023, Online
Dec. 14-16, 2023
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