Phase 2 SUMMIT study was a multicohort basket trial to evaluate the safety and efficacy of neratinib in patients with activating EGFR exon 18 or ERBB2 mutation solid tumors. Interim results of pre-treated patients with lung cancer EGFR exon 18 cohort showed single dose of 240 mg neratinib daily met the pre-specified criteria. This cohort enrolled 11 EGFR exon 18 mutant metastatic lung cancer patients with a median of 2 prior lines of therapy, including EGFR TKI: gefitinib, erlotinib, osimertinib, and/or afatinib.
The objective response rate was 40% in pretreated patients(4 out of 10), the median duration of response was 7.5 months (4.0–NE), and the median progression-free survival was 9.1 months (3.7–NA). The safety profile also demonstrated a manageable result: no reports of ≥ grade 3 AEs, 4 patients (36%) reported grade 1, and 1 patient (9%) reported grade 2 diarrhea. EGFR exon 18 mutations are rare (about 5%) in NSCLC adenocarcinomas, and the G719X mutation is the most common. For EGFR rare mutations, a pan-ErbB inhibitor afatinib is often used in clinic; however, the response rate was about 10.5% in NSCLC EGFR G719X TKI pre-treated patients. These early study results indicated that neratinib, another irreversible pan-ErbB TKIs, may provide another option for NSCLC EGFR exon 18 mutations patients once failing front line FDA approved TKI therapy.
News release from Puma Biotechnology, November 6, 2020.
Yang et al. Journal of Thoracic Oncology (2020) 15(5): 803-815