Efficacy and Safety of Anti-Programmed Death-Ligand 1 Monoclonal Antibody Socazolimab With Carboplatin and Etoposide for Extensive-Stage SCLC: Results From the Phase 1b Clinical Trial

Abstract

Introduction: The study (ClinicalTrials.gov, NCT04346914) is an open label, single-arm, phase 1b clinical trial investigating the safety, tolerability, and efficacy of the recombinant human anti-programmed death-ligand 1 monoclonal antibody socazolimab in combination with carboplatin and etoposide in the first-line treatment of extensive-stage SCLC. Good safety and efficacy were found in previous phase 1 clinical trials of other cancers, such as cervix cancer.

Methods: Patients received socazolimab (5 mg/kg) every three weeks until disease progression or physician decision. Carboplatin (area under the curve: 5) was also administered every three weeks and etoposide (100 mg/m²) on days 1, 2, and 3 of the treatment cycle. The primary purpose of the study was safety measured by the Common Terminology Criteria for Adverse Events. Secondary purposes included objective response rate, progression-free survival, duration of response, and overall survival.

Results: From April 15, 2020 (enrollment date), to December 30, 2021 (data cutoff), 20 patients with extensive-stage SCLC were administered with socazolimab, carboplatin, and etoposide. Objective response rate was 70.0% (95% confidence interval [CI]: 45.72%-88.11%). Median progression-free survival was 5.65 months (95% CI: 4.14-6.54), and the median duration of response was 4.29 months (95% CI: 2.76-5.85). Median overall survival was 14.88 months (95% CI: 10.09-not evaluated). The highest incidence of treatment-related adverse events included anemia (100%), decreased neutrophil count (95%), decreased platelet count (95%), and decreased white blood cell count (95%), which occurred during combination therapy. The most common grade 3 or 4 treatment-related adverse events were neutropenia (90%), decreased white blood cell count (65%), decreased platelet count (50%), and anemia (30%), which were also common adverse reactions of chemotherapy. No adverse events leading to death had occurred.

Conclusions: Results revealed that the combination therapy of socazolimab, carboplatin, and etoposide had preliminarily confirmed the safety of socazolimab in the first-line treatment of SCLC combined with EC chemotherapy. Currently, a phase 3, randomized, placebo-controlled trial (ClinicalTrials.gov, NCT04878016) is being conducted with 498 patients.

Keywords: Carboplatin; Etoposide; Extensive-stage small cell lung cancer (ES-SCLC); PD-L1; Socazolimab.

Figure 1

Patient disposition. HBV, hepatitis B virus.

Figure 2

(A) Change of tumor burden from baseline (investigator assessed; n = 20). Bar length is decrease or increase in target lesion size. Bar color is best overall response. (B) Change from baseline over time (investigator assessed; n = 20) for each individual. (C) Treatment exposure and response duration (by RECIST version 1.1; investigator assessed; n = 20). The length of each bar corresponds to the duration of treatment. Response symbols represent time to first report and not best overall. CR, complete response; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease.

Figure 3

(A) Kaplan-Meier curve for patient progression-free survival (full analysis set). (B) Kaplan-Meier curve for overall survival (full analysis set). EC, etoposide and carboplatin.