Phase II randomized study of ramucirumab plus pembrolizumab versus standard of care for advanced non-small cell lung cancer previously treated with a checkpoint inhibitor: Toxicity update (Lung-MAP non-matched sub-study S1800A).
Authors: Karen L. Reckamp, Mary Weber Redman, Konstantin H. Dragnev, Liza C. Villaruz, Bryan A. Faller, Tareq Al Baghdadi, Susan Hines, Lu Qian, Katherine Minichiello, David R. Gandara, Roy S. Herbst, Karen Kelly
Journal: Journal of Clinical Oncology (2021)

9075 Background: The therapeutic landscape in metastatic NSCLC has dramatically changed with approvals of immunotherapy agents in both treatment-naïve and previously treated cancer patients (pts) and irrespective of histology. Pts with tumors that develop resistance is a significant area of unmet need. Vascular endothelial growth factor (VEGF) has been shown to modulate the tumor immune microenvironment and combination immune checkpoint and VEGF/VEGF receptor inhibition have shown benefit in multiple tumor types. Lung-MAP is a master protocol for pts with stage IV, previously treated NSCLC. Pts who were not eligible for a biomarker-matched substudy enrolled in S1800A. The adverse event profile will be presented. Methods: S1800A is a phase II randomized trial for pts who previously received PD-1 or PD-L1 inhibitor therapy for at least 84 days and platinum-based doublet therapy with ECOG 0-1 stratified by PD-L1 expression, histology and intent to receive ramucirumab in the standard of care (SOC) arm. Pts were randomized 1:1 to pembrolizumab and ramucirumab P+R or SOC (docetaxel +R [SOC w R]; docetaxel, pemetrexed or gemcitabine [SOC wo R]). The primary endpoint was overall survival. Secondary endpoints included response, duration of response, investigator assessed-progression free survival and evaluation of toxicity. Results: From May 17, 2019 to November 16, 2020, 166 pts enrolled and 140 determined eligible [69 (49%) P+R; 46 (33%) SOC w R; 25 (18%) SOC wo R]. Treatments for those who received SOC wo R included 3 on docetaxel (19%); 12 on gemcitabine (75%); and on 1 on pemetrexed (6%). 131 were eligible for adverse event (AE) assessment. The most common AE were fatigue (38%), proteinuria (28%), hypertension (23%), diarrhea (22%) and hypothyroidism (22%) on P+R; fatigue (61%), anemia (48%), diarrhea (41%) and neutropenia (39%) on SOC w R and anemia (56%), leukopenia (56%), fatigue (44%) and neutropenia (44%) on SOC wo R. Grade ≥ 3 treatment-related AEs occurred in 32% of pts on P+R, 54% of pts on SOC w R and 56% of pts on SOC wo R. Cardiac and thromboembolic events occurred in 12% of pts on P+R, 11% of pts on SOC w R and 0% of pts on SOC wo R. Grade 5 AE occurred in 2 pts on P+R (respiratory failure and cardiac arrest), 3 pts on SOC w R (2 respiratory failure and sepsis) and 1 pt on SOC wo R (sepsis). Four patients were diagnosed with COVID-19 (1 on P+R and 3 on SOC) and 3 died (1 on P+R and 2 on SOC). Conclusions: Grade 3 toxicities were lower in P+R compared to SOC arms with or without R. Cardiac and thromboembolic events were similar in arms that included R. P+R was generally well-tolerated. Efficacy outcomes will be presented when data matures. Clinical trial information: NCT03971474.