Phase II study of afatinib plus pembrolizumab in patients with squamous cell carcinoma of the lung following progression during or after first-line chemotherapy (LUX-Lung-IO).

Afatinib and pembrolizumab have separately shown survival benefit in patients with squamous cell carcinoma (SqCC) of the lung, and there is biological rationale for concurrent inhibition of the programmed death ligand-1 and epidermal growth factor receptor (EGFR) pathways in this patient population. This open-label, single-arm study enrolled patients with SqCC of the lung who had progressed during/after first-line chemotherapy and comprised two parts: a safety run-in to establish the recommended phase II dose (RP2D; afatinib 40 mg or 30 mg once daily with pembrolizumab 200 mg every 3 weeks); and the main part assessing efficacy and safety of the RP2D. The primary endpoint was objective response rate (ORR); secondary endpoints included the RP2D, progression-free survival (PFS) and overall survival (OS). Twenty-four patients were treated in the safety run-in (afatinib 40 mg/30 mg cohorts: n = 12/12). Median age was 63.5 years; 79.2% of patients were male. All patients discontinued afatinib and pembrolizumab, most commonly due to disease progression (58.3% and 75.0%, respectively) or adverse events (AEs; 37.5% and 25.0%, respectively). The study was discontinued early after completion of the safety run-in, and no patients entered the main part. ORR was 12.5%; median PFS and OS were 13.1 and 29.3 weeks, respectively. All patients had ≥ 1 drug-related AE (grade ≥ 3: 45.8%). While there were no new or unexpected safety findings, exploratory analysis of antitumor activity indicated limited efficacy with afatinib plus pembrolizumab in patients with SqCC of the lung who had progressed during/after first-line chemotherapy. NCT03157089.

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