As reported in the Journal of Clinical Oncology by Jänne et al, an interim analysis of the phase III EXCLAIM-2 trial showed no progression-free survival benefit with mobocertinib—an EGFR tyrosine kinase inhibitor (TKI) targeting EGFR exon 20 insertion (ex20ins) mutations—compared with platinum-based chemotherapy as first-line treatment in patients with advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations.
Study Details
In the international open-label trial, 354 patients were randomly assigned between January 2020 and December 2022 to receive mobocertinib at 160 mg once daily (n = 179) or pemetrexed plus cisplatin (n = 19) or carboplatin (n = 144) every 3 weeks for four cycles followed by maintenance pemetrexed (n = 175). Approximately 55% of patients in each group were Asian. The primary endpoint was progression-free survival on blinded independent central review.
Key Findings
Median follow-up was 13 to 14 months. Median progression-free survival was 9.6 months (95% confidence interval [CI] = 7.1–11.1 months) in the mobocertinib group vs 9.6 months (95% CI = 7.2–11.4 months) in the chemotherapy group (hazard ratio [HR] = 1.04, 95% CI = 0.77–1.39, P = .803); the prespecified futility boundary of HR > 1 was crossed and the study was discontinued.
Confirmed objective response rate was 32% (95% CI = 26%–40%) in the mobocertinib group vs 30% (95% CI = 24%–38%) in the chemotherapy group, with median durations of response of 12.0 vs 8.4 months. On quality-of-life assessment, clinically meaningful delays in time to deterioration of lung cancer symptoms, cognitive function, and constipation were observed in the mobocertinib group.
Common grade ≥ 3 adverse events in the mobocertinib group vs the chemotherapy group included diarrhea (20% vs 1%), anemia (6% vs 10%), increased lipase (6% vs 0%), and decreased neutrophils (1% vs 7%).
The investigators concluded: “The EXCLAIM-2 trial did not meet its primary endpoint. The efficacy of mobocertinib was not superior to platinum-based chemotherapy for first-line treatment of patients with [EGFR exon 20 insertion–positive] advanced/metastatic NSCLC.”
Tony S.K. Mok, MD, of Chinese University of Hong Kong, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Takeda Development Center Americas, Inc. For full disclosures of the study authors, visit ascopubs.org.
