Efficacy and safety of lurbinectedin as second-line therapy in Chinese patients with small cell lung cancer: Preliminary results of a phase 1 study.

Abstract

8580 Background: Lurbinectedin (Zepzelca), a selective inhibitor of oncogenic transcription, was granted accelerated approval on June 15, 2020, by the FDA for adult patients (pts) with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy, based on the results from SCLC cohort in PM1183-B-005-14 trial. Here we report the preliminary results of a phase 1 study (LY01017/CT-CHN-101) which aimed to evaluate the safety, tolerability, pharmacokinetics (PK) characters and preliminary efficacy of lurbinectedin in Chinese pts with advanced solid tumors including relapsed SCLC. Methods: In the dose-escalation stage, 10 pts with advanced solid tumors received lurbinectedin (2.5-3.2 mg/m2) as 1-hour i.v. infusion q3wk in a classical 3+3 design, without primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during Cycle 1. In the dose-expansion stage, 22 pts with relapsed SCLC after first-line platinum-based chemotherapy were treated with single-agent lurbinectedin at the recommended dose (RD) defined in the dose-escalation stage, with or without G-CSF support. Endpoints included safety (CTCAE v5.0), tolerability, PK, and confirmed objective response rate (ORR; RECIST v1.1). The data cutoff was January 13, 2022. Results: No dose-limiting toxicity (DLT) was observed in the first 3 pts treated at 2.5 mg/m2, while 1/7 pts treated at 3.2 mg/m2 had DLT (grade 4 neutropenia lasting ≥3 days) in Cycle 1, thus 3.2mg/m2 without G-CSF prophylaxis was defined as the RD of the dose-expansion stage. At cutoff, 22 SCLC pts treated in the dose-expansion stage were still ongoing, with 21 and 22 pts evaluable for efficacy and safety, respectively. The investigator-assessed confirmed ORR was 42.9% (9/21, partial responses). The duration of response (DOR) is pending. The most common grade 3-4 treatment-related adverse events (TRAEs) were neutropenia (16 [72.7%]), leukopenia (13 [59.1%]), thrombocytopenia (9 [40.9%]), increased ALT (4 [18.2%]), anemia (3 [13.6%]), and increased AST (2 [9.1%]). Serious treatment-related adverse events, including neutropenia (5 [22.7%]), leukopenia (4 [18.2%]), thrombocytopenia (3 [13.6%]), increased ALT (2 [9.1%]), increased AST (2 [9.1%]), vomiting (2 [9.1%]), febrile neutropenia (1 [4.5%]), and edema (1 [4.5%]), were reported in 10 pts (45.5%). No cases of infection, sepsis and Hy’s law were reported. A total of 40.9% (9/22) had dose delay and 31.8% (7/22) had dose reduction, mainly attributed to hematological toxicities. No discontinuations occurred due to AEs. No treatment-related deaths were reported. Conclusions: Lurbinectedin at the RD (3.2mg/m2) shows promising efficacy as second-line therapy in Chinese pts with SCLC, with acceptable tolerability and manageable safety profile. Clinical trial information: NCT04638491.