Mobosetinib/mobosetinib cannot improve PFS and chemotherapy in EGFR exon 20+ NSCLC

According to data from the phase 3 EXCLAIM-2 trial (NCT04129502), in patients with advanced or metastatic EGFR exon 20 insertion mutations non-small cell lung cancer (N In patients with SCLC, first-line drug mobocertinib does not meet the primary endpoint of progression-free survival (PFS) compared with platinum-based chemotherapy

According to Blinded Independent Central Review (BICR), the median progression-free survival was 9.6 months (95% confidence interval [CI], 7.1-11.1) in the mobotinib group compared with 9.6 months (95% CI, 7.2-11.4) in the chemotherapy group (HR, 1.04; 95% CI: 0.77-1.39; P=0.803). In addition, the median progression-free survival assessed by each investigator was 8.6 months (95% CI, 6.9-9.9) and 8.4 months (95% CI, 7.1-11.1), respectively. The data showed no difference in PFS outcomes between mobotinib and chemotherapy in prespecified subgroups.

Per BICR, the confirmed objective response rate (ORR) for mobotinib was 32% (95% CI, 26%-40%), compared with an ORR of 30% for chemotherapy % (95% CI, 24%-38%); according to the investigator's assessment, the corresponding incidence rates were 37% (95% CI, 30%-45%) and 30% (95% CI, 24%-38%) respectively. Additionally, the median time to response was 1.5 months per arm and 2.8 months per BICR. According to BICR, the median duration of response (DOR) was 12.0 months (95% CI, 8.5-23.6) and 8.4 months (95% CI, 5.7-11.0), respectively.

The data highlighted that the median overall survival (OS) in the mobotinib arm could not be estimated (NE; 95% CI, 22.6-NE), compared with 30.0 months (95% CI, 29.0-NE) in the chemotherapy arm (HR, 0.98; 95% CI: 0.62-1.54). In each group, the OS rates at 2 years were 61% (95% CI, 49%-71%) and 62% (95% CI, 50%-73%), and at 3 years they were 51% (95% CI, 36%-64%) and 47% (95% CI, 30%-63%). Mobotinib is not better than platinum-based chemotherapy as a first-line treatment for EGFR [exon 20 insertion positive] NSCLC. The primary endpoint [PFS] crossed the prespecified futility limit and the trial was terminated early.

In open tagsIn the phase 3 EXCLAIM-2 trial, a total of 354 patients were randomly assigned to receive mobotinib 160 mg once daily (n = 179) or pemetrexed plus cisplatin or carboplatin every 3 weeks for 4 cycles, followed by pemetrexed maintenance therapy (n = 175). The primary endpoint of the trial was PFS based on BICR based on RECIST v1.1 criteria. Secondary endpoints include confirmed ORR, OS, DOR, time to response, time to deterioration (TTD), and health-related quality of life.

Patients 18 years of age and older with histologically or cytologically confirmed locally advanced, recurrent, or metastatic nonsquamous NSCLC and documented EGFR exon 20 insertion mutations are eligible to participate in this study. 2 Additional eligibility criteria include 1 or more measurable lesions per RECIST v1.1 guidelines, life expectancy of 3 months or more, ECOG performance status of 0 or 1, and good organ and blood function.

According toEORTC QLQ-LC13 composite lung cancer symptom score, the median TTD was 9.4 months in the mobotinib treatment group and 5.0 months in the chemotherapy group. The event rates in each group were 46% and 56% respectively (HR, 0.68; 95% CI, 0.50-0.93). Additionally, 84% and 12% of patients experienced diarrheal events (HR, 16.73; 95% CI, 10.21-27.41), 52% and 34% of patients experienced anorexia events (HR: 1.90; 95% CI: 1.35-2.68), and 9% and 38% reported constipation events (HR; 0.185; 95% CI; 0.105-0.328).

At least 1 treatment-emergent adverse effect (AE) of any grade occurred in 99% of the mobotinib group and 98% of the chemotherapy group, with 62% and 53% of patients in each group experiencing a grade 3 or higher event. Across treatment groups, 36% and 25% of patients, respectively, experienced serious TEAEs, with 77% and 63% experiencing TEAEs leading to dose adjustments, 70% and 6% experiencing dose interruptions, 45% and 20% experiencing dose reductions, and 18% and 20% discontinuing treatment.

The most common any-grade TEAEs in the mobotinib and chemotherapy groups included diarrhea (96% vs. 18%), paronychia (47% vs. 1%), decreased appetite (43% vs. 29%), stomatitis (40% vs. 14%), nausea (37% vs. 47%), and acneiform dermatitis (35% vs. 2%). Additionally, the most common grade 3 or higher TEAEs were diarrhea (20%) in the mobotinib group and anemia (10%) in the chemotherapy group.

References:https://www.cancernetwork.com/view/mobocertinib-does-not-improve-pfs-vs-chemotherapy-in-egfr-exon-20-nsclc