NSCLC

Summit Therapeutics plans a Q4 2025 BLA submission for ivonescimab plus chemotherapy in EGFR-mutated NSCLC based on positive Phase III HARMONi trial results. A new Phase III CRC study (HARMONi-GI3) will begin, with more Phase III trials planned. HARMONi showed a 48% reduction in disease progression risk in NSCLC and the HARMONi-6 study in China demonstrated a 40% reduction in risk in squamous NSCLC compared to tislelizumab plus chemotherapy. The HARMONi-3 study will analyze squamous and non-squamous NSCLC cohorts separately.

Taiho Oncology and Cullinan Therapeutics presented data at ESMO 2025 on zipalertinib, an EGFR tyrosine kinase inhibitor, for NSCLC patients with EGFR exon 20 insertion or uncommon mutations and CNS involvement. The REZILIENT2 study showed a 31.3% intracranial ORR and 68.8% iDCR in patients with measurable CNS disease treated with zipalertinib. Median intracranial DOR was 8.1 months. The drug demonstrated manageable side effects. These results suggest potential for zipalertinib in treating this patient population with limited options, warranting further investigation.

Summit Therapeutics announced positive Phase III HARMONi trial data for ivonescimab plus chemotherapy in EGFR-mutated NSCLC patients who progressed after EGFR-TKI treatment. While the primary analysis showed a positive OS trend (HR=0.79, p=0.057), longer follow-up of Western patients demonstrated improved OS (HR=0.78, p=0.0332). North American patients showed a promising OS HR of 0.70. Ivonescimab’s safety profile was consistent with prior studies. A conference call will be held September 8, 2025, to discuss these findings.

The TROPION-Lung02 and TROPION-Lung04 trials support DATROWAY (datopotamab deruxtecan) combined with immunotherapy as a first-line treatment for advanced NSCLC. TROPION-Lung02 showed a 54.8% objective response rate with DATROWAY and pembrolizumab. Exploratory analyses show promising biomarker associations and the TROPION-Lung04 study found a 57.5% objective response rate when using DATROWAY with rilvegostomig. NeoCOAST-2 data also revealed positive results in the neoadjuvant setting.