Site Editor
Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Monday, April 14, 2025
First-line treatment with the EGFR tyrosine kinase inhibitor mobocertinib failed to show superiority to a platinum-based chemotherapy strategy in patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) and an EGFR exon 20 insertion mutation, based on interim results from the confirmatory phase III EXCLAIM-2 trial published in the Journal of Clinical Oncology. According to Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues, the safety and tolerability of mobocertinib were consistent with previous reports.
“Although EXCLAIM-2 did not meet its primary endpoint, the results provide additional supportive evidence of [the] clinical activity with mobocertinib…shown in the phase I/II study that led to [its] accelerated approval,” the investigators commented. “The mobocertinib accelerated approval experience highlights the need to thoroughly assess the pros and cons of potential study designs of phase III confirmatory trials for full regulatory approval.”
Patients were randomly assigned in a 1:1 ratio to receive 160 mg of mobocertinib once daily (n = 179) or pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by maintenance pemetrexed (n = 175). At interim analysis, the median blinded independent central review–assessed progression-free survival was 9.6 months in both arms (hazard ratio [HR] = 1.04; P = .803); thus, the primary endpoint crossed the prespecified futility boundary (HR > 1), and the study was discontinued.
The blinded independent central review–assessed confirmed objective response rate was 32% with mobocertinib vs 30% with chemotherapy; the median duration of response was 12.0 months vs 8.4 months, respectively. Based on quality-of-life assessments, treatment with mobocertinib resulted in clinically meaningful delays in the time to deterioration of lung cancer symptoms, cognitive function, and constipation. The most frequently reported adverse events of grade 3 or higher were diarrhea (mobocertinib: 20%; chemotherapy: 1%), anemia (6% vs 10%), increased lipase levels (6% vs 0%), and decreased neutrophil counts (1% vs 7%).
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
