Serplulimab-chemo shows promise for squamous NSCLC

Patients with previously untreated, locally advanced, or metastatic squamous non-small-cell lung cancer (NSCLC) may derive benefit from the addition of the novel anti-PD-1 monoclonal antibody serplulimab to chemotherapy, according to the final analysis of the phase III ASTRUM-004 study.

“Compared with placebo, first-line serplulimab plus chemotherapy significantly improved survival [in these patients and had] a manageable safety profile,” said Professor Caicun Zhou from the Shanghai Pulmonary Hospital in China, during his presentation at WCLC 2023.

The study comprised 537 patients (median age 63 years, 91 percent male) with histologically or cytologically confirmed stage IIIB/C or IV squamous NSCLC and no prior systemic therapy. Participants were randomized 2:1 to receive IV serplulimab 4.5 mg/kg or placebo (up to 35 cycles) in combination with chemotherapy (carboplatin AUC* 5 or 6 and nab-paclitaxel 100 mg/m² Q3W for four to six cycles). This was followed by serplulimab or placebo maintenance for up to 2 years or until disease progression or intolerable toxicity. [WCLC 2023, abstract OA09.05]

In the assessment by the independent radiologic review committee, the progression-free survival (PFS) benefit of serplulimab over placebo was sustained after a median follow-up of 31.1 months (median 8.3 vs 5.7 months; stratified hazard ratio [HR], 0.55, 95 percent confidence interval [CI], 0.43–0.69; p<0.001).

Except for the subset of patients with liver metastasis, the updated PFS consistently favoured serplulimab-chemo across most prespecified subgroups, with HRs ranging between 0.43 and 0.94.

Overall survival was significantly longer in the serplulimab vs the placebo arm (median 22.7 vs 18.2 months; stratified HR, 0.73, 95 percent CI, 0.58–0.93; p=0.010), which crossed the significance boundary of 0.046.

In the two-stage model adjusted for crossover (54 percent crossed over from placebo to serplulimab), the adjusted HR for OS was 0.49 (95 percent CI, 0.37–0.64).

Serplulimab also outdid placebo in terms of confirmed objective response rate (60.1 percent vs 40.8 percent) and duration of response (median 11.1 vs 5.5 months; stratified HR, 0.45, 95 percent CI, 0.32–0.65). Complete and partial response rates with serplulimab were 56.7 percent and 3.4 percent, respectively; the corresponding rates in the placebo arm were 40.2 percent and 0.6 percent.

A third of participants reported having grade ≥3 treatment-related adverse events (AEs) with serplulimab and placebo (35.5 percent and 31.8 percent), the most frequent being decreased neutrophil count (14.8 percent and 14.5 percent), anaemia (12.0 percent and 10.6 percent), and decreased white blood cell count (10.1 percent and 11.2 percent).

Immune-related AE (irAE) rate was higher in the serplulimab vs placebo arm (29.6 percent vs 17.3 percent). The most common irAEs were hypothyroidism (6.4 percent vs 0.6 percent) and rash (5.0 percent vs 1.1 percent).

These results imply that the experimental regimen had a manageable safety profile, with no new safety signals observed during the trial, noted Zhou.

A standard of care for squamous NSCLC

Up to 30 percent of NSCLC cases are the squamous type, with low frequency of targetable gene alterations. [J Thorac Oncol 2018;13:165-183; J Cancer Ther 2020;11:365-370; J Thorac Oncol 2016;11:1411-1422]

“Preferred treatment options with a favourable risk-benefit ratio [for squamous NSCLC] are still limited in the global setting,” said Zhou. “[These findings imply that the] serplulimab-chemo regimen represents a promising treatment option for this patient subset.”

“The findings reaffirm that chemotherapy plus PD-(L)1 inhibitors are a standard of care for patients with advanced squamous NSCLC,” noted discussant Dr Justin Gainor from the Massachusetts General Hospital, Boston, Massachusetts, US.

Serplulimab has been approved by the National Medical Products Administration of China for squamous NSCLC, extensive-stage SCLC, and MSI-H** solid tumours.