Abstract 1047P
Background
Resistance develops following treatment with immune checkpoint inhibitor (ICI) therapy for non-small cell lung cancer (NSCLC), even after initial stabilization or response. Vascular endothelial growth factor receptor (VEGFR) and ICI therapy has demonstrated benefit across solid tumor types. We showed improved overall survival (OS) with pembrolizumab and ramucirumab (P+R) compared to standard-of-care (SOC) following progression on prior platinum-based doublet and ICI in patients with advanced NSCLC (HR: 0.69, 1-sided p-value=0.05. We evaluate OS in an exploratory analysis based on prior ICI response and duration of previous ICI.
Methods
S1800A was a randomized phase II trial for patients who were ineligible for a biomarker-matched substudy with acquired resistance to ICI defined as previous ICI therapy for at least 84 days with progressive disease (PD) on or after therapy. 137 patients were eligible and randomized to receive P+R or SOC (investigator’s choice of docetaxel/ramucirumab, docetaxel, pemetrexed or gemcitabine). The primary analysis compared OS at the 1-sided 10% level log-rank test. OS in each group was compared between the arms by prior response to ICI and duration of ICI therapy using a Cox Model.
Results
Best prior response on ICI in patients receiving P+R was PR in 29%, SD in 57%, PD in 13%; SOC had 41% PR, 41% SD and 18% PD (Figure 1). Time on prior ICI <6 months in 28% on P+R, 35% on SOC; 6-12 months in 46% on P+R, 38% on SOC; ≥12 months in 26% P+R, 27% SOC. A trend toward improved OS with P+R was seen in patients with PR or SD with a similar HR to the overall population; patients with prior PD had less benefit. Patients who received prior ICI <6 months or ≥12 months demonstrated a favorable OS benefit, the 6-12 month group requires additional analysis.
Conclusions
Treatment with ramucirumab and pembrolizumab significantly increased OS compared to SOC in advanced NSCLC following progression on prior ICI. In this exploratory analysis, consistent OS benefits were observed irrespective of time on treatment or prior response to ICI suggesting a biological benefit from the combination in patients who develop acquired resistance to ICI. A larger randomized trial is required to confirm these findings.
Clinical trial identification
NCT03971474.
Editorial acknowledgement
Legal entity responsible for the study
Southwest Oncology Group (SWOG).
Funding
Funded by National Institutes of Health/National Cancer Institute grant awards U10CA180888, U10CA180819, U10CA180821, UG1CA233323, UG1CA189830, UG1CA189971, UG1CA189858, UG1CA233340; Foundation for the National Institutes of Health; and in part by Eli Lilly and Company and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, Eli Lilly and Company and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
K. Reckamp: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Blueprint, Daiichi Sankyo, EMD Soreno, Genentech, GlaxoSmithKline, Janssen, Lilly, Merck KGA, Mirati, Seattle Genetics, Takeda, Tesaro; Financial Interests, Institutional, Principal Investigator: Genentech; Blueprint; Calithera; Daiichi Sankyo; Elevation Oncology; Janssen. All other authors have declared no conflicts of interest.