Abstract 1269P
Background
Programmed cell death-1/ligand 1 (PD-1/PD-L1) inhibitors have become key treatment options for advanced NSCLC without EGFR, ALK, or ROS1 mutations. Here, we report on the antitumour activity of cemiplimab, an anti–PD-1, alone or plus ipilimumab (an anti-cytotoxic T-lymphocyte-associated protein 4 agent) in second-line (2L) advanced NSCLC.
Methods
Patients with advanced NSCLC were randomised (1:1:1; stratified by histology and PD-L1 status) to receive cemiplimab 350 mg once every 3 weeks (Q3W) (Arm A); or cemiplimab 350 mg Q3W plus ipilimumab 50 mg once every 6 weeks (Q6W) (up to 4 doses) (Arm B); or cemiplimab 1050 mg Q3W (Arm C), for up to 108 weeks or until disease progression. Primary endpoint was objective response rate (ORR) in patients with PD-L1 expression <50%, per independent central review. Data cut-off was 28 Aug 2019.
Results
Of 28 patients enrolled, 27 received treatment (Arm A, n=8; Arm B, n=11; and Arm C, n=8). Median (range) age was 68 (46–80) years; 71.4% were male; 39.3% had prior radiotherapy; 67.9% had non-squamous NSCLC; and 57.1% had a PD-1 level <1%. Median duration of treatment exposure was 10.8 (Arm A), 17.9 (Arm B), and 10.8 (Arm C) weeks. ORR (95% confidence interval) was 0% (0.0–36.9%) in Arm A, 45.5% (16.7–76.6%) in Arm B and 11.1% (0.3–48.2%) in Arm C. For patients with PD-L1 levels <1%, ORR was 36.4% (Arm B), and 11.1% (Arm C); for patients with PD-L1 levels of 1–49%, ORR was 9.1% (Arm B), and 0% (Arm C). Median duration of response (DOR) has not been reached; observed DOR was 2+ to 6.9+ (Arm B) and 4.8+ months (Arm C). Most common treatment-emergent adverse events of any grade were decreased appetite and constipation (each 37.5%) in Arm A; hypothyroidism and pneumonia (each 36.4%) in Arm B; and decreased appetite (37.5%) in Arm C. Across all arms, increased alanine aminotransferase was the only Grade ≥3 immune-related adverse event reported in >1 patient (Arm B; 18.2%).
Conclusions
In patients with advanced NSCLC and <50% PD-L1 expression, 2L combination treatment with cemiplimab 350 mg + ipilimumab 50 mg exhibited numerically higher antitumour activity than cemiplimab monotherapy (350 or 1050 mg).
Clinical trial identification
NCT03430063.
Editorial acknowledgement
Medical writing support was provided by Atif Riaz, PhD of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi.
Legal entity responsible for the study
Regeneron Pharmaceuticals, Inc. and Sanofi.
Funding
Regeneron Pharmaceuticals, Inc. and Sanofi.
Disclosure
S. Lee: Shareholder/Stockholder/Stock options, Full/Part-time employment: Regeneron Pharmaceuticals, Inc. J. de Castro Carpeño: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Hoffmann-la Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp and Dohme; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer ; Advisory/Consultancy: Takeda. M.M. Tarruella: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Kyowa Kirin; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. Y. Summers: Advisory/Consultancy: Bristol-Myers Squibb. Y. Xu, I. Lowy, P. Rietschel: Shareholder/Stockholder/Stock options, Full/Part-time employment: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.