Subcutaneous administration of the anti-PD-1 monoclonal antibody toripalimab achieves similar drug exposure as the intravenous formulation in advanced non-squamous non-small cell lung cancer (NSCLC), with similar efficacy and safety outcomes, suggested a Chinese trial.

As such, the subcutaneous formulation “offers a valuable and alternative treatment option that may reduce patient burden and benefit resource allocation in healthcare systems,” said study presenter Lin Wu, MD, at the European Lung Cancer Congress (ELCC) 2026 on March 27.

The current phase 3 trial involved adult patients with untreated recurrent or metastatic non-squamous NSCLC who had measurable disease and no EGFR-sensitive mutations or ALK fusions, explained Wu, of the Second Department of Thoracic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University in Changsha, China. The study participants were randomly assigned to four cycles of subcutaneous toripalimab 360 mg or intravenous toripalimab 240 mg, with both groups also receiving platinum-based chemotherapy in the form of pemetrexed, carboplatin, and cisplatin. All patients then entered a maintenance phase consisting of either subcutaneous or intravenous toripalimab plus pemetrexed until disease progression or intolerable toxicity.

Commenting on the findings, Mariano Provencio, MD, PhD, chair of the Medical Oncology Department, Puerta de Hierro University Hospital, Madrid, Spain, who was not involved in the trial, described it as “clinically relevant, particularly from a regulatory and practical standpoint” and said the results confirm exposure to toripalimab is noninferior with subcutaneous administration.

However, he cautions that the results are “not definitive” because the follow-up period was short, and it is not clear whether the tumor assessments were investigator-assessed or also underwent independent central review.

Provencio said he would also like to see data on responses stratified by PD-L1 expression, particularly in patients with a poor prognosis, such as those with liver metastases, as well as more detailed safety outcomes.

Study Methods and Results

In all, 396 patients were randomly assigned, with 198 patients in both the subcutaneous and intravenous groups. They had a median age of 62.0 years and 63.0 years, respectively, and 75.8% and 85.4% were male. The majority (88.4% and 90.4%) had stage IV disease.

The primary objective of the study was to compare the pharmacokinetics resulting from the two administrative routes, and so the primary endpoints were the serum concentration (C_trough) at the end of cycle 1 and the population pharmacokinetic model-simulated area under the receiver operating characteristics curve (AUC) from 0 to 21 days (AUC_0-21 day) during cycle 1.

The geometric mean ratios for observed C_trough and model-predicted AUC_0-21 day were 1.30 and 0.91, respectively, confirming the noninferior exposure of subcutaneous vs intravenous toripalimab, Wu said.

He continued that, after a median follow-up of 7.2 months, “comparable efficacy was observed in the two arms, at an overall response rate of 57.6% with subcutaneous toripalimab and 49.5% with intravenous administration.

Median progression-free survival was 8.1 months for both subcutaneous and intravenous administration, and the 6-month progression-free survival rate was 59.3% vs 56.8%. Six-month overall survival was 90.6% vs 88.2% with subcutaneous toripalimab vs intravenous administration.

Intravenous toripalimab plus chemotherapy has been approved in China for the first-line treatment of advanced, non-squamous NSCLC, Wu said.

In the US, toripalimab has been approved by the FDA in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or with recurrent, locally advanced nasopharyngeal carcinoma (NPC) and as a single agent for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after a platinum-containing chemotherapy.

Adverse Events

Grade ≥ 3 treatment-related adverse events (TRAEs) occurred in 37.9% vs 40.1% of patients receiving subcutaneous vs intravenous toripalimab, while grade ≥ 3 immune-related adverse events were seen in 6.6% vs 7.1% of patients. TRAEs leading to discontinuation were reported in 5.1% vs 4.6% of patients, and there was a TRAE that led to death in the intravenous arm.

The most common adverse events were anemia, neutropenia, and leukopenia, which occurred at similar rates in the two treatment arms.

The study was funded by Shanghai Junshi Bioscience Co., Ltd.

Wu declared having no relevant financial relationships. Provencio declared having relationships with Bristol Myers Squibb, Roche, AstraZeneca, Merck Sharp & Dohme, Takeda, Boehringer Ingelheim, Celgene, Thermo Fisher, Janssen, Amgen, PharmaMar, and Qiu.