This is the most aggressive subtype of lung cancer and those with the extensive stage disease (ES-SCLC) have rapid tumour growth and a poor prognosis. Treatment is typically with etoposide plus platinum chemotherapy but, again, the prognosis is poor.
Immune checkpoint inhibitors offer an alternative, notably anti-PD-L1 monoclonal antibodies. It was, however, unknown whether adding a PD-1 inhibitor to the therapeutic regimen instead of an anti-PD-L1 inhibitor would be an effective alternative.
A PD-1 inhibitor, serplulimab, is being developed by Shanghai Henlius Biotech and tested both as a monotherapy and in combination with standard chemotherapy. The humanised IgG4 monoclonal antibody is being investigated in various solid tumours, including ES-SCLC.
In an open label Phase I study in recurrent solid tumours, subjects in the first dose-finding part were given 0.3, 1.0, 3.0 or 10.0 mg/kg of the antibody every 2 weeks via intravenous infusion until disease progression, withdrawal, death or a year had elapsed.1
In a dose expansion cohort, patients were given fixed doses of 200, 300 or 400 mg every 2, 3 or 4 weeks, respectively. It was well tolerated up to 10.0 mg/kg, with a disease control rate of 60%, an objective response rate of 8.0% and a median progression-free survival of 107 days.
A Phase II trial has also been done in patients with unresectable or metastatic microsatellite instability high (MSIH) or mismatch repair deficient solid tumours.2 Subjects were given 3.0 mg/kg of serplulimab every 2 weeks for up to 2 years.
At an interim analysis, 108 patients had been given at least one dose and 68 patients with confirmed MSIH were included in the main efficacy analysis population, with a 13.5-month median follow-up duration. The objective response rate in these patients was 39.7%, with three complete responses.
In the sensitivity analysis population of 58 patients, the figures were 43.1% and two, respectively. Median duration of response, progression-free survival and overall survival were not reached; the 12-month overall survival rate was 74.5%.
Results of a double-blind, randomised Phase III study in ES-SCLC patients have also been reported.3 It enrolled 585 participants with ES-SCLC who had not previously been given systemic therapy; they were randomised to receive 4.5 mg/kg of serplulimab or a placebo intravenously every 3 weeks (in addition to intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks).
Median overall survival was significantly longer for those given serplulimab, at 15.4 months, compared with the placebo (10.9 months). Median progression-free survival was also longer with the antibody (5.7 months compared with 4.3 months with the placebo).
Treatment-related adverse events at grade 3 or higher occurred in 33.2% of antibody patients and 27.6% of those given the placebo. Trials continue.
References
- C-L. Ho, et al., J. Clin. Oncol. 40(Suppl. 16), Abstr. e14560 (2022).
- J. Li, et al., J. Clin. Oncol. 40(Suppl. 16), Abstr. 2592 (2022).
- Y. Cheng, et al., JAMA 328, 1223 (2022).