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
Published report from the trial registered as NCT04129502, in Journal of Clinical Oncology (2025), chosen as the most cited paper whose own text cites the registry id.
Overview
Purpose: Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets EGFR exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2, ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of EGFR ex20ins+ advanced/metastatic NSCLC.
Methods: Patients with treatment-naive EGFR ex20ins+ locally advanced/metastatic NSCLC were randomly assigned 1:1 to mobocertinib 160 mg once daily or pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by maintenance pemetrexed. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR), with planned interim analysis (IA) after approximately 70% of 227 expected PFS events.
Results: A total of 354 patients were randomly assigned (mobocertinib: n = 179; chemotherapy: n = 175). Baseline characteristics were balanced between arms. At IA (cutoff: April 4, 2023), the median PFS per BICR was 9.6 months in each treatment arm (hazard ratio [HR], 1.04 [95% CI, 0.77 to 1.39]; P =.803). The primary end point crossed the prespecified futility boundary (HR > 1). The confirmed objective response rate (95% CI) per BICR was 32% (26 to 40) with mobocertinib versus 30% (24 to 38) with chemotherapy; the median duration of response was 12.0 versus 8.4 months. Quality-of-life assessments indicated clinically meaningful delays in time to deterioration of lung cancer symptoms, cognitive function, and constipation with mobocertinib versus chemotherapy. Grade ≥3 adverse events in >5% of patients (mobocertinib, chemotherapy) were diarrhea (20%, 1%), anemia (6%, 10%), increased lipase (6%, 0%), and decreased neutrophil count (1%, 7%).
Conclusion: The EXCLAIM-2 trial did not meet its primary end point. The efficacy of mobocertinib was not superior to platinum-based chemotherapy for first-line treatment of patients with EGFR ex20ins+ advanced/metastatic NSCLC.
Indexed on Europe PMC as PubMed record 39879577 (DOI 10.1200/jco-24-01269). Its abstract cites the registry id NCT04129502, which is how it was matched to this trial; no figure has been checked by an editor.
This is the paper Europe PMC returns for registry id NCT04129502 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.