September 2026 NCCN NSCLC Update Adds Sevabertinib to Precision Therapy
核心洞察
The September 2026 NCCN update to metastatic NSCLC guidance adds sevabertinib (搜索) as a first-line targeted option for HER2 (搜索)-mutated advanced disease after its FDA accelerated approval on September 9, 2026.
Daraxonrasib, an oral RAS(ON) multiselective inhibitor, enters the NCCN emerging-biomarker framework for previously treated KRAS (搜索)-mutant NSCLC involving G12, G13 and Q61 alterations, though it remains off-label in lung cancer.
In SOHO-01, sevabertinib (搜索) produced a confirmed objective response rate of 75% among 69 previously untreated patients with HER2 (搜索) tyrosine kinase domain mutations, with 73% of responders in response at six months.
The September 2026 update to the NCCN framework for metastatic non-small cell lung cancer (搜索) adds sevabertinib (搜索) (Hyrnuo) as a first-line targeted option for HER2 (搜索)-mutated advanced disease, following expansion of its FDA indication on September 9, 2026. The accelerated approval covers adults with locally advanced or metastatic non-squamous NSCLC harboring HER2/ERBB2 tyrosine kinase domain activating mutations detected by an FDA-authorized test, and it removed the prior requirement for systemic therapy, permitting use in treatment-naive disease. The companion diagnostic covers activating ERBB2 alterations including single-nucleotide variants in exons 18 to 21 and exon 20 insertions.
The approval is supported by SOHO-01, in which 69 previously untreated patients with locally advanced or metastatic HER2 (搜索) TKD-mutated NSCLC had a confirmed objective response rate of 75% (95% CI 64% to 85%); 73% of responders remained in response at six months and 38% at 12 months. A randomized confirmatory study, SOHO-02, is intended to verify benefit in previously untreated advanced HER2-mutant NSCLC.
Daraxonrasib, formerly RMC-6236, enters the NCCN emerging-biomarker table for KRAS (搜索) alterations at G12, G13 and Q61 codons at a 200 mg once-daily phase II dose, but is not FDA approved for NSCLC and remains off-label. The phase I/II RMC-6236-001 study, published in September 2026 in the New England Journal of Medicine, reported a 42% confirmed objective response rate, 89% disease-control rate, 11.5-month median duration of response, 8.3-month median progression-free survival and 16.0-month median overall survival in 38 docetaxel-naive patients treated at 160 to 220 mg after platinum chemotherapy and anti-PD-1/PD-L1 therapy. Grade 3 or higher adverse events occurred in 54% of patients treated at 300 mg or less, with rash, diarrhea, nausea, vomiting and mucositis or stomatitis among common toxicities. RASolve 301 is comparing daraxonrasib with docetaxel in previously treated RAS-mutant NSCLC.
The update also lists capmatinib, tepotinib and crizotinib for high-level MET amplification, where a copy number of at least 10 by NGS is consistent with high-level amplification, and erdafitinib for potentially oncogenic FGFR (搜索) mutations or fusions.