Aim: Tepotinib + osimertinib has shown promising efficacy in patients with EGFRm METamp NSCLC, who have a high unmet medical need after 1L osimertinib. We report the primary analysis of tepotinib + osimertinib from INSIGHT 2 (NCT03940703) in patients with ≥9 months’ follow-up (data-cut: March 28, 2023).
Methods: Patients with advanced EGFRm METamp NSCLC detected by FISH tissue biopsy (TBx) and/or by NGS liquid biopsy (LBx), following progression on 1L osimertinib received tepotinib 500 mg (450 mg active moiety) + osimertinib 80 mg once daily. Primary endpoint was objective response by IRC in patients with FISH+ METamp.
Results: Of 481 patients pre-screened, METamp was identified by FISH TBx in 169 (35%) patients and by NGS LBx in 52 (11%) patients. A total of 128 patients received tepotinib + osimertinib (median [m] age 61 years [range 20–84], 57.8% female, 61.7% Asian, 67.2% never smoker, 72.7% ECOG PS 1).
In 98 patients with FISH+METamp, ORR was 50.0% (95% CI: 39.7, 60.3). mDOR was 8.5 months (95% CI: 6.1, NE), mPFS was 5.6 months (95% CI: 4.2, 8.1), and mOS was 17.8 (11.1, NE). Outcomes were also meaningful in patients with LBx NGS+METamp; ORR, mDOR, mPFS, and mOS were 54.8% (95% CI: 36.0, 72.7), 5.7 months (2.9, 15.4), 5.5 months (2.7, 7.2), and 13.7 months (2.9, 15.4), respectively.
In 128 patients treated with tepotinib + osimertinib, the most common TRAEs were diarrhea in 63 (49.2%; Grade ≥3, 1 [0.8%]) and peripheral edema in 52 (40.6%; Grade ≥3, 6 [4.7%]) patients. Thirteen patients (10.2%) discontinued treatment due to TRAEs; pneumonitis (n = 6 [4.7%]) was the most common reason.
Conclusions: Tepotinib + osimertinib exhibited durable efficacy and a tolerable safety profile, making it a potential chemotherapy-sparing oral targeted therapy option in patients with EGFRm METamp NSCLC after 1L osimertinib.