Envafolimab plus docetaxel in combination with or without trilaciclib versus docetaxel in pretreated advanced or metastatic non-small cell lung cancer (NSCLC): Preliminary analysis of an open-label, randomized, phase II trial.

e20562 Background: For patients with advanced NSCLC who fail first-line chemotherapy combined with immunotherapy, docetaxel as standard second line treatment often yields disappointing results. Immune rechallenge with alternative immune checkpoint inhibitors(ICIs) may enhance efficacy. Trilaciclib, a CDK4/6 inhibitor, protects hematopoietic stem cells during chemotherapy and potentially exhibits immune-enhancing properties when combined with ICIs. Further research is needed to explore trilaciclib's potential in improving the outcomes of second-line treatment combinations in advanced NSCLC. Methods: This prospective, multicenter, open-label, randomized, phase II trial was conducted at five centers in China in patients with advanced NSCLC who had failed the first-line treatment with platinum-based chemotherapy combined with PD-1 inhibitors. Patients were randomly assigned (1:1:1) to receive trilaciclib (240 mg/m 2 ) before docetaxel (intravenous infusion of 75 mg/m 2 ), and envafolimab (300 mg, subcutaneous injection) every 3 weeks in cohort A, docetaxel and envafolimab in cohort B, docetaxel alone in cohort C until disease progression, unacceptable toxicity, or death (whichever occurred first). The primary endpoint was PFS. Results: As of December 12, 2024, a total of 25 pts were enrolled, with 10 in cohort A, 8 in cohort B, and 7 in cohort C. Among the 25 pts, 17 pts underwent at least one efficacy evaluation. In cohort A, 7/10(70%) pts achieved stable disease(SD); in cohort B, 1/8(12.5%) achieved partial response (PR) and 2/8(25%) achieved SD; and in cohort C, 2/7(28.6%) achieved SD. Hematological toxicity occurred in 17/25 (68%) pts during the first cycle, with a lower incidence in cohort A compared to cohorts B and C. Conclusions: Trilacilib prior to envafolimab and docetaxel yielded potential clinical efficacy, and trilacilib may help alleviate the hematological toxicity of combination therapy in the second-line treatment of advanced NSCLC. PFS data, OS data and and myeloprotection with trilaciclib will be updated in the future. Clinical trial information: NCT05910034 . Antitumor efficacy and hematological adverse events during the first treatment cycle. CohortA(n=10) CohortB(n=8) CohortC(n=7) Antitumor Efficacy, n(%) BOR PR 0 1 (12.5) 0 SD 7 (70.0) 2 (25.0) 2 (28.6) PD 1 (10.0) 1 (12.5) 3 (42.9) NE 2 (20.0) 4 (50.0) 2 (28.6) ORR 0 1 (12.5) 0 DCR 7 (70.0) 3 (37.5) 2 (28.6) Hematological Adverse Events, n(%) Neutropenia 5 (50.0) 5 (62.5) 6 (85.7) ≥ Grade 3 Neutropenia, n(%) 4 (40.0) 4 (50) 5 (71.4) Anemia, n(%) 1 (10.0) 1 (12.5) 3 (42.8) ≥ Grade 3 Anemia, n(%) 0 0 0 Thrombocytopenia, n(%) 1 (10.0) 1 (12.5) 0 ≥ Grade 3 Thrombocytopenia, n(%) 0 0 0 Double hematological events, n(%) 2 (20.0) 2 (25.0) 4 (57.1)