EXCLAIM-2
Trial question
What is the role of mobocertinib in patients with EGFR exon 20 insertion-positive advanced/metastatic non-small cell lung cancer?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
63.0% female
37.0% male
N = 354
354 patients (224 female, 130 male).
Inclusion criteria: patients with EGFR exon 20 insertion-positive advanced/metastatic non-small cell lung cancer.
Key exclusion criteria: untreated symptomatic brain metastases; symptomatic or asymptomatic spinal cord compression or leptomeningeal disease; previous systemic treatment for locally advanced or metastatic disease; radiotherapy ≤ 14 days before randomization.
Interventions
N=179 mobocertinib (at a dose of 160 mg/day).
N=175 chemotherapy (pemetrexed plus cisplatin or carboplatin every 3 weeks for 4 cycles followed by maintenance pemetrexed).
Primary outcome
Median progression-free survival
9.6 months
9.6 months
9.6 months
7.2 months
4.8 months
2.4 months
0.0 months
Mobocertinib
Chemotherapy
No significant
difference ↔
No significant difference in median progression-free survival (9.6 months vs. 9.6 months; HR 0.96, 96% CI 0.72 to 1.3).
Secondary outcomes
No significant difference in overall survival (78% vs. 78%; HR 1.02, 95% CI 0.65 to 1.61).
Significant increase in median duration of response (12 months vs. 8.4 months; HR 2.1, 95% CI 1.14 to 3.85).
Safety outcomes
No significant difference in treatment-emergent adverse events.
Conclusion
In patients with EGFR exon 20 insertion-positive advanced/metastatic non-small cell lung cancer, mobocertinib was not superior to chemotherapy with respect to median progression-free survival.
Reference
Pasi A Jänne, Bin-Chao Wang, Byoung Chul Cho et al. First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial. J Clin Oncol. 2025 May;43(13):1553-1563.
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