OA15.01 Mobocertinib in EGFR Exon 20 Insertion–Positive Metastatic NSCLC Patients With Disease Control on Prior EGFR TKI Therapy

Abstract

EGFR exon 20 insertions (ex20ins) occur in 4%–10% of EGFR mutations in non–small cell lung cancer (NSCLC), accounting for ∼2% of NSCLC. No approved therapies specifically for EGFR ex20ins+ NSCLC are available. Objective response rates (ORRs) in previously treated patients receiving first-, second-, or third-generation EGFR tyrosine kinase inhibitors (TKIs) are <10%, with a median progression-free survival (PFS) <4 months. Mobocertinib (TAK-788), an oral EGFR TKI that specifically targets EGFR with ex20ins, holds Breakthrough Therapy Designation for patients with EGFR ex20ins+ NSCLC who previously progressed on platinum-based chemotherapy (in the United States) or who had prior chemotherapy (in China), based on preliminary phase 1/2 results. A phase 1/2, open-label, multicenter, study of mobocertinib (NCT02716116) evaluated a dose-expansion EGFR ex20ins+ metastatic NSCLC cohort who progressed after response or stable disease for ≥6 months on any prior EGFR TKI therapy. The primary endpoint was confirmed ORR assessed by the investigator per RECIST v1.1. Other efficacy endpoints included disease control rate (DCR), duration of response (DoR), PFS (per Independent Review Committee [IRC]) and investigator, and overall survival (OS). Patients received mobocertinib 160 mg orally once daily. Twenty patients previously treated with EGFR TKI were enrolled, with median age of 61.0 y [range: 38–78] and Eastern Cooperative Oncology Group performance status of 0 (35%) or 1 (65%); 55% female. Median number of metastatic sites was 3.5 (range: 1–6); 10 patients (50%) had baseline brain metastases. Sixteen patients (80%) received prior platinum-based chemotherapy and 13 patients (65%) received prior immunotherapy. Prior EGFR TKIs included poziotinib (n=13), erlotinib (n=5), afatinib (n=4), and osimertinib (n=4); 11/20 patients (55%) received EGFR TKIs as most recent prior treatment. Confirmed ORR was 20% per investigator and 40% per IRC (Table) and 95% (19/20) had target lesion reduction per IRC. Treatment-related adverse events (TRAEs) observed in ≥20% of patients were diarrhea (90%), nausea (35%), pruritus (30%), rash (25%), anemia (25%), vomiting (20%), dermatitis acneiform (20%), and fatigue (20%). Grades 3/4 TRAEs occurred in 4 patients (20%). Serious AEs occurred in 7 patients (35%). Two patients discontinued due to AEs (10%).TableEfficacy ParameterN=20Median follow-up, mo14.2Median time on treatment (range), mo7.8 (2–21)Confirmed ORR per IRC, n (%) [95% CI]8 (40) [19.1–63.9]Confirmed ORR per investigator, n (%) [95% CI]4 (20) [5.7–43.7]Median DoR per IRC, mo [95% CI]13.0 [5.6–not reached]Confirmed DCR per IRC, n (%) [95% CI]18 (90) [68.3–98.8]Median PFS per IRC, mo [95% CI]7.3 [3.6–13.0]Median OS, mo [95% CI]Not reached [14.7–not reached]6-mo OS rate, %94.712-mo OS rate, %78.6Confirmed ORR per IRC in patients previously treated with TKI targeting EGFR exon 20 (poziotinib), n/N (%)*4/13 (31)Confirmed ORR per IRC in patients previously treated with other EGFR TKIs (afatinib, osimertinib, erlotinib), n/N (%)*4/7 (57)*Patients may have received ≥1 TKI. Open table in a new tab *Patients may have received ≥1 TKI. Mobocertinib treatment had a clinically meaningful benefit for patients with EGFR ex20ins+ metastatic NSCLC with ≥6-month disease control on prior EGFR TKI. The safety profile was manageable, similar to other patient cohorts, and consistent with the broader class of EGFR TKIs.