Lung-MAP S1800A: ramucirumab plus pembrolizumab

S1800A was the first Lung-MAP sub-study designed for patients whose non-small-cell lung cancer had progressed after immune checkpoint therapy, a group with no good standard. It randomised 166 patients to ramucirumab with pembrolizumab or to standard of care (docetaxel with or without ramucirumab, gemcitabine or pemetrexed), with overall survival as the primary endpoint of a phase 2 designed to detect a large signal.

Karen Reckamp and colleagues reported in the Journal of Clinical Oncology in 2022 that median overall survival was 14.5 months with the combination against 11.6 months with standard care, a hazard ratio of 0.69, with fewer severe side effects. Response rates were similar in both arms, so the benefit appeared to come from disease control rather than shrinkage, and progression-free survival was not significantly different.

Because a phase 2 survival signal in 166 patients is not proof, SWOG and the NCI opened Pragmatica-Lung (S2302), a deliberately simple phase 3 with minimal eligibility rules and data collection, to confirm the result in a population close to routine practice. S1800A also became the model for Lung-MAP's later immunotherapy-combination sub-studies in patients who have already had checkpoint blockade.