Lung-MAP S1800E: A randomized phase II/III study of docetaxel and ramucirumab with or without cemiplimab for patients previously treated with platinum-based chemotherapy and immunotherapy for stage IV or recurrent non-small cell lung cancer (NSCLC).

Abstract

TPS8669 Background: Integration of immunotherapy into first line systemic therapy for patients with metastatic NSCLC has led to improvement in survival, but most patients experience disease progression. Blockade of PD-1 and VEGFR2 synergistically inhibits tumor growth by reducing tumor neovascularization and leads to upregulation of proinflammatory cytokines. We hypothesize that continuing second line anti-PD-1 therapy using cemiplimab in combination with docetaxel and ramucirumab may reverse immunotherapy resistance, and lead to improved overall survival (OS) compared to docetaxel and ramucirumab. Methods: Lung-MAP is a master protocol for patients with previously treated advanced NSCLC. S1800E is a phase II/III non-match Lung-MAP substudy, in which patients are randomized 1:1 to receive either standard of care treatment with intravenous docetaxel and ramucirumab (arm A) or investigational treatment with intravenous docetaxel and ramucirumab in combination with cemiplimab (arm B). The primary objective is to compare OS between patients assigned to arm A and arm B who have acquired resistance to platinum-based chemotherapy and immunotherapy for Stage IV or recurrent NSCLC. The total enrollment goal is 378 patients based on a design with 90% power to rule out an HR = 1 at the 1-sided 2.5% level, if the true HR = 0.66. The design includes 3 interim analyses, with a safety run-in for the first 10 patients on arm B. The main inclusion criteria are patients who experienced disease progression 84 days or more following initiation of anti-PD-(L)1 immunotherapy, with complete response, partial response or stable disease as their best response, in addition to progression on or following platinum-based chemotherapy. If a known sensitizing molecular alteration for which an FDA-approved targeted therapy for NSCLC exists (e.g., EGFR, ALK, ROS1, BRAF, RET, NTRK, KRAS, HER2 , and MET sensitizing mutations), patients must have previously received at least one line of targeted therapy. Prior docetaxel is not permitted, and there is a washout of 14 days from palliative radiation (shortened to 7 days for bone radiation) and 28 days from major surgery, with no plans for concurrent systemic therapy while on the clinical trial. Patients must have adequate organ and marrow function and ECOG performance status of 0-1. S1800E was activated on 4/28/2025, with first patient registered on 5/22/2025. As of 1/6/2026, 49 of the planned 378 patients have been enrolled. Clinical trial information: NCT06616584 .