A Phase 1b clinical trial has indicated that socazolimab, a PD-L1 monoclonal antibody, combined with etoposide and carboplatin (EC), shows potential survival benefits in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). The study, conducted across three centers in China, evaluated the safety and tolerability of the combination therapy in 20 patients.
Study Design and Objectives
The primary objective of the study was to assess the safety of socazolimab in combination with EC, measured by the incidence and severity of adverse events. Secondary endpoints included investigator-assessed objective response rate (ORR), progression-free survival (PFS), disease control rate, overall survival (OS), and duration of response (DOR).
Efficacy and Survival
The trial reported a median PFS of 5.65 months (95% CI: 4.14–6.54) and a median OS of 14.88 months (95% CI: 10.09–NE). While three patients with asymptomatic brain metastasis were enrolled, their PFS and OS were shorter than those without brain metastasis. These findings suggest that socazolimab combined with chemotherapy may offer a survival advantage in the first-line treatment of ES-SCLC.
PD-L1 Expression and Immunogenicity
All patients provided tissue samples for PD-L1 expression analysis. All tested samples were positive for PD-L1. The study explored the correlation between PD-L1 expression and survival outcomes; however, due to the small sample size, no definitive correlation could be established. The immunogenicity of socazolimab was also evaluated by assessing the presence of anti-drug antibodies (ADAs). ADAs were detected in five patients, a higher incidence compared to some other PD-1/PD-L1 monoclonal antibodies, but similar to atezolizumab. No marked difference in safety or response time was observed between ADA-positive and ADA-negative patients.
Safety and Tolerability
The incidence of treatment-related adverse events (TRAEs), particularly grade 3 or 4, was higher than that reported in foreign studies of similar drugs. Most grade 3 or 4 TRAEs occurred during the combination treatment period, with myelosuppression being the most common. During single-agent maintenance therapy with socazolimab, grade 3 or 4 TRAEs were rare, indicating a favorable safety profile. Infusion reactions were observed in six patients, occurring at the start of etoposide infusion. These reactions were alleviated with symptomatic treatment and a decreased infusion rate. One patient discontinued treatment due to grade 2 arrhythmia.
Implications and Future Directions
This Phase 1b study provides preliminary evidence supporting the safety and efficacy of socazolimab in combination with EC chemotherapy for the first-line treatment of SCLC. The ongoing Phase 3 study (NCT04878016) is expected to further validate these findings. The results suggest that socazolimab has the potential to achieve survival benefits in ES-SCLC patients. Further studies could include giving patients oral nonsteroidal anti-inflammatory drugs, analgesic drugs, and antihistamines, or adding low-dose corticosteroids after the completion of socazolimab infusion and before the use of chemotherapy drugs.
