A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non-small cell lung cancer and progressive disease (PD) after immunotherapy (Anti-PD-1/PD-L1 inhibitor) alone or in combinati

<h2>Abstract</h2><h3>Background</h3> Immune checkpoint inhibitor (ICI)-based treatment regimens have become the standard of care for first-line treatment of NSCLC. Once progressed, it is not recommended to continue using ICI monotherapy, and the efficacy of chemotherapy is limited (ORR ∼10% with doc), so there is a high unmet clinical need. Plin is a selective immunomodulating microtubule-binding agent which promotes dendritic cell maturation and enhances anti-tumor T cell response, and have the potential to overcome immunotherapy resistance as a novel regimen in combination with pemb and doc. This phase 2 study was aimed to evaluate the efficacy and safety of pemb plus plin and doc in pts with metastatic NSCLC who had progressed after ICI. <h3>Methods</h3> In this investigator-initiated, single-arm, open-label, phase 2 trial, metastatic NSCLC pts who acquired resistance after ICI treatment were enrolled (Clinical trial information: NCT05599789). Participants received pemb 200 mg D1, plin 30 mg/m2 D1 and doc 75 mg/m2 D1 intravenously for a 21-day cycle. The primary endpoint was investigator-based ORR per RECIST 1.1. The secondary endpoints included PFS, OS, DoR and toxicity. Kaplan-Meier method is used for OS, PFS, and DOR analysis. The study intends to enroll 47 patients with a formal interim analysis at 19 patients enrolled. <h3>Findings</h3> 38 pts were enrolled and 35 pts evaluable ITT population were analyzed at data cutoff on 10/10/2024. Median follow-up was 8.8 months (M) and median age was 68.0 (50-83) with 77.1% male and 22.9% female. 65.7% were current or former smokers. Histology included 60% with non-squamous, 40% with squamous cell carcinoma. Confirmed ORR was 18.2%. DCR was 89.7% (defined as PR and SD > 4 M), median DoR was 11.4 M, median PFS was 8.3 M (current 6 M PFS rate was 70.4%, 12 M PFS rate was 42.7%), and OS had not been reached. 48.6% of pts experienced G3 or higher treatment-related AEs. <h3>Interpretation</h3> With good tolerability, pemb plus plin and doc in pts with metastatic NSCLC who progressed after clinical benefit to ICI demonstrated promising efficacy.