ASTRUM-004: Serplulimab Plus Chemotherapy as First-Line Treatment of Advanced Squamous Non–Small Cell Lung Cancer

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A novel treatment approach to squamous non–small cell lung cancer (NSCLC) may improve the prognosis for patients with previously limited treatment options, according to data presented at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer.1 Findings from the phase III ASTRUM-004 study showed significant increases in overall survival and progression-free survival with carboplatin/nab-paclitaxel plus the novel anti–PD-1 monoclonal antibody serplulimab vs placebo in previously untreated patients with locally advanced or metastatic squamous NSCLC.

“This combination regimen represents a new treatment option for this patient population in the global setting,” said lead study author Caicun Zhou, MD, Professor, Shanghai Pulmonary Hospital, China. “Based on these results, serplulimab plus chemotherapy should be the new standard of care for advanced squamous non–small cell lung cancer.”

Caicun Zhou, MD

Caicun Zhou, MD

As Dr. Zhou explained, more people die of lung cancer than any other cancer type around the world. Squamous NSCLC accounts for up to 30% of NSCLC cases,1 but these cancers have a low frequency of targetable gene alterations,2 and existing treatment options with a favorable risk-benefit ratio are still limited in the global setting.

Adding a PD-1/PD-L1 inhibitor to chemotherapy, however, has demonstrated improved outcomes in the first-line setting.3 The use of serplulimab has improved survival in patients with various tumor types and has been approved by the China Food and Drug Administration for microsatellite instability–high solid tumors, extensive-stage small cell lung cancer, and squamous NSCLC.

Study Details

For the randomized, double-blind, multicenter, ASTRUM-004 trial, patients with histologically or cytologically confirmed stage IIIB/IIIC or IV squamous NSCLC and no prior systemic therapy were included. They were randomly assigned to receive intravenous serplulimab (4.5 mg/kg) or placebo (up to 35 cycles) in combination with chemotherapy (carboplatin and nab- paclitaxel, 4–6 cycles) in 3-week cycles. Randomization was stratified by PD-L1 expression level (tumor proportion score [TPS] < 1% vs 1% ≤ TPS < 50% vs TPS ≥ 50%).

Authors of the study reported that patient characteristics were balanced between treatment arms. The median patient age was 63, and most patients were male, Asian, and had stage IV disease. Most patients were also former smokers (64% of the experimental group, 68% of the control group), and a significant portion of patients were current smokers (22% of the experimental group, 21% of the control group).


  • First-line treatment with chemotherapy plus the anti–PD-1 monoclonal antibody serplulimab vs placebo improved overall survival and progression-free survival in patients with advanced squamous NSCLC, according to results of the phase III ASTRUM-004 trial.
  • According to the study investigators, the regimen demonstrated a good safety profile and was well tolerated by the patient population.

With 31.1 months of follow-up, serplulimab plus carboplatin/nab-paclitaxel showed consistent benefits in overall survival, progression-free survival, overall response rate, and duration of response. The median overall survival with serplulimab plus chemotherapy was observed to be 22.7 months vs 18.2 months with placebo plus chemotherapy (hazard ratio [HR] = 0.73; P = .010). Likewise, progression-free survival was also improved with the serplulimab combination, with a median of 8.3 months compared with 5.7 months in the control group (HR = 0.55; P < .001).In addition, the tumor response rate increased from 41% in the placebo arm to 60% in the serplulimab arm. The medium duration of response was also nearly doubled in the experimental arm vs the control arm (HR = 0.45).

In terms of safety, serplulimab plus carboplatin/nab-paclitaxel demonstrated a manageable profile, with no new safety signals being observed during the study duration, according to the investigators. Rates of grade 3 and 4 adverse events remained largely the same across the experimental and control arms, with 33% and 27% of patients experiencing serious treatment-related adverse events, respectively. 

DISCLOSURE: Dr. Zhou reported no conflicts of interest.


1. Zhou C, Hu Y, Arkania E, et al: A phase 3 study of serplulimab plus chemotherapy as first-line treatment for squamous non-small-cell lung cancer (ASTRUM-004). 2023 World Conference on Lung Cancer. Abstract OA09.05. Presented September 11, 2023.

2. Socinski MA, Obasaju C, Gandara D, et al: Current and emergent therapy options for advanced squamous cell lung cancer. J Thorac Oncol 13:165-183, 2018.

3. Yakobson A, Mor T, Dina L, et al: ROS1 in squamous non-small cell lung cancer—Combined immunotherapy (PD1/CTLA4) or targeted therapy? J Cancer Ther 11:365-370, 2020.


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