INSIGHT 2: Tepotinib plus osimertinib in patients with EGFR-mutant NSCLC having acquired resistance to EGFR TKIs due to MET-amplification: A phase II trial in progress study

Abstract

Background: In MYSTIC, an open-label, phase 3 trial of first-line D (anti-PD-L1) ± T (anti-CTLA-4) vs CT, while not statistically significant, a clinically meaningful improvement in overall survival (OS) was seen with D vs CT in patients with tumour cell PD-L1 expression >25% (TC > 25% [primary analysis population]; D vs CT, HR 0.76 [97.54% CI 0.56-1.02]; D+TvsCT, HR 0.85 [98.77% CI 0.61-1.17]). Here we report results in a subpopulation of Asian patients. Methods: Immunotherapy/CT-naïve patients with metastatic NSCLC were randomized (1:1:1) to D (20 mg/kg q4w); D (20mg/kgq4w) + T (1 mg/kgq4w <4 doses); or CT. In this analysis in a subpopulation of Asian patients, efficacy outcomes were evaluated in patients with PD-L1 TC >25%; safety was evaluated in all treated patients (regardless of PD-L1 expression). Results: Of the 488 patients in the primary analysis population (PD-L1 TC>25%), 156 (32%) were Asian (D, 59; D+T, 50; CT, 47). Baseline characteristics in the Asian population were balanced between treatment arms. OS was improved in Asian patients (PD-L1 TC >25%) withD vsCT (HR 0.69 [95% CI 0.43-1.09]) and D+T vs CT (HR 0.64 95% CI 0.40-1.03]); more patients receiving D or D+T remained in response at 6 months vs CT (Table). Grade >3 treatment-related adverse events (TRAEs) and any grade TRAEs leading to discontinuation occurred in 19.7% and 9.0% (D); 23.9% and 14.5% (D+T); 23.4% and 7.2% (CT) patients in the Asian subpopulation, respectively. Conclusions: Durvalumab resulted in a favourable HR for OS compared to CT in patients with PD-L1 TC>25% in the Asian subpopulation, which was consistent with the primary analysis population. OS HR for D+T vs CT appeared to be more favourable in the Asian subpopulation compared to the primary analysis population, although results should be interpreted with caution due to small sample sizes. The safety profile of D6T in the subpopulation of Asian patients was manageable and consistent with the primary analysis population.