507O EXCLAIM-2: Phase III trial of first-line (1L) mobocertinib versus platinum-based chemotherapy in patients (pts) with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins)+ locally advanced/metastatic NSCLC

Mobocertinib is approved for patients with EGFR ex20ins+ advanced NSCLC following failure of platinum-based chemotherapy, with a manageable safety profile. We report results from EXCLAIM-2 comparing 1L mobocertinib with platinum-based chemotherapy in EGFR ex20ins+ advanced/metastatic NSCLC. This open-label, multicenter study (NCT04129502) randomized pts with untreated EGFR ex20ins+ locally advanced/metastatic NSCLC to (1:1) mobocertinib 160 mg PO daily or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2/carboplatin AUC 5 IV every 3 weeks for 4 cycles followed by maintenance pemetrexed. Response was assessed per RECIST v1.1. The primary endpoint was progression-free survival (PFS) assessed by blinded independent review committee (BIRC), with a planned interim analysis (IA) after 184 events. A total of 354 pts were randomized (mobocertinib 179; chemotherapy 175). Baseline characteristics were balanced between arms. At IA (data cutoff April 4, 2023), BIRC-assessed median PFS was similar between arms (mobocertinib 9.59 mo; chemotherapy 9.63 mo), with BIRC PFS hazard ratio [HR]=1.038 and P=0.803. The study met prespecified futility criteria (BIRC PFS HR >1). BIRC confirmed objective response rates were (mobocertinib/chemotherapy) 32%/30%, confirmed disease control rates were 87%/80%, and median duration of response was 12 vs 8 mo. Grade ≥3 adverse events (AEs) occurred in 62%/53% of pts. Discontinuations due to death (3%/1%) or AEs (10%/14%) were similar between arms (additional safety in the table). Delay in time to deterioration of lung cancer symptoms per EORTC QLQ-LC13 was noted with mobocertinib. At IA, mobocertinib efficacy was similar but not superior to 1L platinum-based chemotherapy. Safety profiles were similar to previous reports, with no new safety concerns identified.Table: 507OEXCLAIM-2 safety summaryMobocertinib n=179Chemotherapy n=163aTEAEs, %9998Grade ≥36253Serious3625Leading to study drugDiscontinuation1820Interruption706Reduction4520Modification7763Related9995TEAEs ≥25% in either arm, %Diarrhea9618Paronychia471Decreased appetite4329Stomatitis4014Nausea3747Dermatitis acneiform352Dry skin345Fatigue3134Increased blood creatinine307Increased lipase305Anemia2942Vomiting2626Increased amylase255Increased alanine aminotransferase1828Increased aspartate aminotransferase1627Constipation1248a12 pts randomized to chemotherapy did not receive treatment.TEAE, treatment-emergent adverse events. Open table in a new tab