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Abstract
Background 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),1 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.2 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.
Methods 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.
Results 36 pts were enrolled and 30 pts evaluable ITT population were analyzed at data cutoff on 8/29/2024. Median follow-up was 11.5 months (M) and median age was 68.0 (50–77) years with 73.3% male and 26.7% female. 60% were current or former smokers. Histology included 57% with non-squamous, 43% with squamous cell carcinoma. Confirmed ORR was 21.4%. DCR was 89.3% (defined as PR and SD > 4 M), median DoR was 11.4 M, median PFS was 8.6 M (current 6 M PFS rate was 71.3%, 12 M PFS rate was 41.9%), and OS had not been reached. 48.3% of pts experienced G3 or higher treatment-related AEs.
Conclusions With good tolerability, pemb plus plin and doc in pts with metastatic NSCLC who progressed after clinical benefit to ICI demonstrated promising efficacy with doubled ORR, doubled PFS, and tripled DCR compared with historical controls of chemotherapy.
Acknowledgements The study was funded by MSD R&D (China) Co., Ltd., Beijing, China and Dalian Wanchun Bulin Pharmaceutical Co., Ltd., Liaoning, China. We thank all patients, their families, and the institutions for supporting this study.
Trial Registration Clinical trial information: NCT05599789.
References
X Pu, et al. Anlotinib plus docetaxel vs. docetaxel alone for advanced non-small-cell lung cancer patients who failed first-line treatment: a multicenter, randomized phase II trial. Lung Cancer 2024;191:107538.https://doi.org/10.1016/j.lungcan.2024.107538.
Liu, et al. Study protocol of KeyPemls-004: 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 (PD-1/PD-L1 inhibitor) alone or in combination with platinum-doublet chemotherapy. Thorac Cancer. 2023:1–6.https://doi.org/10.1111/1759-7714.14806.
Ethics Approval This study was approved by Peking Union Medical College Hospital’s Ethics Board; approval number I-22PJ575.
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