A multicenter, randomized, double-blind, placebo-controlled phase 3 study has demonstrated that socazolimab, a fully human IgG1 monoclonal antibody targeting PD-L1, in combination with etoposide and carboplatin (EC), significantly improves overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). The study, involving 498 patients across 54 hospitals in China, showed a statistically significant and clinically meaningful benefit with the addition of socazolimab to standard chemotherapy.
Improved Overall Survival
The median OS in the socazolimab plus EC group was 13.90 months (95% CI, 12.22–15.34) compared to 11.58 months (95% CI, 10.64–12.81) in the placebo plus EC group. This represents a 2.32-month increase in median survival and a 20.1% reduction in the risk of death (HR, 0.799; 95% CI, 0.652–0.979, one-sided p = 0.0158).
Secondary Endpoints
In addition to the primary endpoint of OS, the study also met its key secondary endpoints. The median progression-free survival (PFS) assessed by the Independent Radiology Committee (IRC) was 5.55 months (95% CI, 5.06–5.82) in the socazolimab plus EC group compared to 4.37 months (95% CI, 4.27–4.70) in the placebo plus EC group (HR, 0.569; 95% CI, 0.457–0.708, p < 0.0001). The objective response rate (ORR) was 75.5% (95% CI, 69.5–80.9) in the socazolimab plus EC group and 68.1% (95% CI, 61.7–74.0) in the placebo plus EC group. The duration of response (DoR) was 4.44 months (95% CI, 4.11–5.32) in the socazolimab plus EC group and 3.45 months (95% CI, 3.06–4.11) in the placebo plus EC group.
Safety Profile
The safety profile of socazolimab plus EC was consistent with previous studies of similar therapies. Treatment-related adverse events (TRAEs) of grade 3 or higher were observed in 80.3% of patients in the socazolimab plus EC group and 75.7% in the placebo plus EC group. The most common TRAEs of grade 3 or higher were hematological toxicities, including decreased neutrophil count, leukocytopenia, decreased platelet count, and anemia. Immune-related adverse events (irAEs) were reported in 19.3% of patients in the socazolimab plus EC group and 9.7% in the placebo plus EC group.
Clinical Implications
These findings suggest that socazolimab in combination with EC represents a new first-line treatment option for patients with ES-SCLC. The observed improvement in OS, PFS, and DoR, coupled with a manageable safety profile, supports the use of this combination therapy in clinical practice. "The addition of Socazolimab to chemotherapy improved OS by 2.32 months, and reduced the risk of death by 20.1%," the researchers noted.
Subgroup Analysis
Subgroup analysis revealed that male patients under 65 years of age experienced a particularly pronounced benefit, with socazolimab prolonging OS by 4.33 months compared to the control group (15.7 m vs. 11.37 m). However, female patients did not show the same survival benefit, potentially due to differences in tumor microenvironment, hormone status, and response to subsequent treatments.
Study Limitations
The study has some limitations, including the lack of a head-to-head comparison with other immune checkpoint inhibitors (ICIs) and the limited number of patients with brain metastases enrolled. Additionally, a high proportion of patients in both groups received subsequent anticancer therapies after disease progression, which may have influenced the overall survival outcomes.
Conclusion
Despite these limitations, the results of this phase 3 clinical trial provide compelling evidence that socazolimab plus EC is an effective and well-tolerated first-line treatment option for patients with ES-SCLC. The findings support the integration of socazolimab into the treatment paradigm for this aggressive disease, offering the potential to improve patient outcomes and extend survival.
