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.

introductionImmune checkpoint inhibitor (ICI)-based treatment regimens have become the standard of care for first-line treatment of metastatic epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) wild-type non-small cell lung cancer (NSCLC). Nevertheless, most patients inevitably develop disease progression, and the mechanisms of resistance to first-line immunotherapy are not clear. ICIs in combination with agents targeting other pathways may serve as second-line therapy options. Plinabulin is a selective immunomodulating microtubule-binding agent which inhibits the polymerization of tubulin monomers, with multiple mechanisms to inhibit tumor growth. Clinical studies have demonstrated preliminary the antitumor efficacy of this agent. Therefore, we hypothesize that a combination of plinabulin with programmed death 1 (PD-1) inhibitor and docetaxel may result in higher efficacy and fewer side effects leading to better tolerance.

methodsIn this investigator-initiated, single-arm, open-label, phase II trial, metastatic NSCLC patients who acquired resistance to first-line immunotherapy-based therapy will be enrolled. Participants will receive pembrolizumab 200 mg D1, plinabulin 30 mg/m DISCUSSION: This trial will provide evidence of the benefit and safety of pembrolizumab in combination with plinabulin and docetaxel in metastatic NSCLC patients who have been exposed and developed resistance to first-line PD-1/PD-L1 inhibitor either as monotherapy or in combination with chemotherapy.