Socazolimab Exhibits Overall Survival Benefit Vs Placebo in ES-SCLC

Overall, treatment with socalizumab vs placebo elicited objective response rates of 75.5% vs 68.1%, respectively, all of which were partial responses.

Socazolimab (ZKAB001) exhibited a statistically significant overall survival (OS) benefit vs placebo when added to chemotherapy containing carboplatin and etoposide as a first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC), according to results from a phase 3 trial (NCT04878016) published in Signal Transduction and Targeted Therapy.1

Efficacy data revealed that at the time of the final analysis 73.4% (n = 182/248) and 80.6% (n = 200/248) of the socazolimab and placebo groups had died. Additionally, the median OS in the respective groups was 13.90 months (95% CI, 12.22-15.34) vs 11.58 months (95% CI, 10.64-12.81), with respective 1- and 2-year OS rates of 56.8% (95% CI, 50.4%-62.7%) vs 48.8% (95% CI, 42.4%-54.8%) and 20.7% (95% CI, 14.8%-27.3%) vs 5.9% (95% CI, 0.8%-18.9%; HR, 0.799; 95% CI, 0.652-0.979, P = .0158).

Furthermore, 62.5% (n = 155/248) and 74.6% (n = 185/248) of the respective groups had experienced disease progression or death at the time of final analysis. The median progression-free survival (PFS) in the socazolimab group was 5.55 months (95% CI, 5.06-5.82) vs 4.37 months (95% CI, 4.27-4.70) in the placebo group (HR, 0.569; 95% CI, 0.457-0.708; P <.0001). Additionally, 75.5% (n = 176) and 68.1% (n = 160) of each group experienced partial responses as a best response and no complete responses, with respective objective response rates (ORRs) of 75.5% (95% CI, 69.5%-80.9%) and 68.1% (95% CI, 61.7%-74.0%).

“[T]he results of this phase 3 clinical trial indicate that socazolimab plus [etoposide/carboplatin] prolongs patient survival time compared to placebo plus [etoposide/carboplatin] in the first-line treatment of [ES-SCLC], without introducing any new safety risk,” Zhiwei Chen, MD, investigator in the Department of Medical Oncology of Shanghai Crest Hospital in the Shanghai Jiao Tong University School of Medicine in Shanghai, China, wrote in the publication with study coinvestigators. “With the increase of product types, physicians can choose treatment plans more flexibly based on the specific clinical conditions of patients.”

Investigators in the double-blind, placebo-controlled multicenter phase 3 study randomly assigned patients 1:1 to receive intravenous carboplatin and etoposide with either socazolimab or matching placebo. All patients were treated with carboplatin given once within the area under the curve serum drug concentration time of 5 mg/ml on day 1 of 21-day cycles, as well as etoposide given continuously at 100 mg/m2 on days 1 to 3 of 21-day cycles.

Patients received the investigational agent at 5 mg/kg intravenously or matching placebo for 2 years or until disease progression, intolerable toxicity, or death. Chemotherapy was administered until 4 cycles were completed or until disease progression, intolerable toxicity, or death. Dose reduction or interruption of chemotherapy was permitted, but dose suspensions for socazolimab or placebo were only allowed for a maximum of 12 weeks.

Patients in the socazolimab and control arms had a median age of 62.8 years (range, 38-79) vs 61.0 years (range, 31-79), and 83.1% vs 82.7% were male. Most patients had stage IV disease (89.1% vs 91.9%), and 4.0% vs 2.8% had brain metastases. Furthermore, most patients had an ECOG performance score of 1 (82.3% vs 82.7%) and a concentration of PD-L1 tumor cells of less than 1% (76.2% vs 78.6%).

The primary end point of the study was OS. Secondary end points included PFS, ORR, duration of response, and safety.

Safety data from the trial revealed that 98.8% of the investigational arm and 98.4% of the control arm experienced treatment-related adverse effects (TRAEs), with grade 3 or higher TRAEs occurring in 80.3% vs 75.7% of the respective groups. The most common grade 3 or higher TRAEs included decreased neutrophil count (69.1% vs 66.8%), leukocytopenia (44.2% vs 34.0%), decreased platelet count (33.7% vs 27.9%), and anemia (23.3% vs 20.6%).

Treatment discontinuations related to TRAEs occurred in 4.8% of the socazolimab group and 2.8% of the placebo group. TRAE-related deaths occurred in 3 patients in the investigational arm and 4 patients in the control arm. In the socazolimab arm, fatal TRAEs included 1 case of acute pancreatitis and 2 cases of unknown cause, and in the control arm, they included 1 instance of heart failure complicated by infectious pneumonia, 1 case of ventricular fibrillation, and 2 cases of unknown cause.

Reference

Chen Z, Chen J, Huang D, et al. A multicenter, randomized, double-blind, placebo-controlled phase 3 study of Socazolimab or placebo combined with carboplatin and etoposide in the first-line treatment of extensive-stage small cell lung cancer. Sig Transduct Target Ther. 2025;10(1):28. doi:10.1038/s41392-024-02115-5