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.

https://bit.ly/3mZL1oy

Yang et al. Journal of Thoracic Oncology (2020) 15(5): 803-815