Roy S. Herbst, MD, PhD, Reviews Ramucirumab Plus Pembrolizumab in ICI-Resistant NSCLC

At 2022 ASCO, Roy S. Herbst, MD, PhD, spoke about the results of a Lung-MAP substudy showing benefit of ramucirumab plus pembrolizumab vs standard of care chemotherapy for patients with advanced non–small cell lung cancer who demonstrated resistance to prior immunotherapy.

At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® spoke with Roy S. Herbst, MD, PhD, Ensign Professor of Medicine and Professor of Pharmacology at Yale School of Medicine and Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital in New Haven, Connecticut, about a nonmatched sub-study of the phase 2 Lung-MAP trial (S1800A; NCT03971474) analyzing ramucirumab (Cyramza) plus pembrolizumab (Keytruda) for patients with advanced non–small cell lung cancer who have been previously treated with immunotherapy.

Herbst examines the design of the trial that enrolled patients with advanced NSCLC and acquired resistance to immunotherapy. The median overall survival in the ramucirumab-plus-pembrolizumab arm was 14.5 months vs 11.6 months in the standard-of-care arm (HR, 0.69; 95% CI, 0.51-0.92; standard log-rank P = .05).


Patients who have failed on immunotherapy were eligible for ramucirumab plus pembrolizumab. That trial, S1800A, was presented by Karen L. Reckamp, MD, on behalf of our team. The results [of this trial] were quite extraordinary. We designed this as a survival trial because we had some prior data to suggest that you don’t always see an improvement in response or progression-free survival with immunotherapy combinations. In fact, that was the case here. If the trial had been designed for progression-free survival, it would have been negative. This was a phase 2, not a phase 3, [trial enrolling between] 140 to 160 patients, so a moderate size trial. This trial could enroll quickly because of the Master Protocol Network that allows patients to be enrolled throughout the country.

We enrolled 6 or 7 patients on [treatment] at the Yale Cancer Center in New Haven, Connecticut, where I work and the results presented at ASCO today showed an improvement in survival by 40%. The survival curve separated almost immediately. The median survival improved by 4 or 5 months with a hazard ratio of 0.61, [equating to almost] a 40% improvement in survival with fewer toxicities in the experimental arm than with standard of care chemotherapy, being a docetaxel-based regimen in most cases. [Patients received] either docetaxel alone or most patients, docetaxel with ramucirumab. This is exciting because if you look [at data from this year’s ASCO] and you know what’s available in the literature, they are very few if, in fact, any combinations that work in this setting. This seems to be a unique setting and one of the great unmet need where we’re seeing some benefits. We’re all excited about it.


Reckamp KL, Redman MW, Dragnev KH, et al. Overall survival from a phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non–small cell lung cancer previously treated with immunotherapy: Lung-MAP nonmatched substudy S1800A. J Clin Oncol. 2022;40(suppl 16):9004. doi: 10.1200/JCO.2022.40.16_suppl.9004