Ociperlimab Plus Tislelizumab Fails to Improve Survival Over Pembrolizumab in PD-L1-High Advanced Non-Small Cell Lung Cancer

Clinical Summary:

• Design/Population: AdvanTIG-302 was a phase 3 trial evaluating first-line ociperlimab plus tislelizumab in patients with previously untreated stage III/IV non-small cell lung cancer and PD-L1 expression of ≥50%. 
• Key Outcomes: Ociperlimab plus tislelizumab did not improve overall survival compared with pembrolizumab. The prespecified interim analysis was terminated for futility.
• Clinical Relevance: Although numerical differences in progression-free survival and overall response rate favored ociperlimab plus tislelizumab, the TIGIT/PD-1 combination did not demonstrate an overall survival advantage over established PD-1 monotherapy. 

Results from the phase 3 AdvanTIG-302 trial showed that combining the investigational TIGIT inhibitor ociperlimab with the PD-1 inhibitor tislelizumab did not improve overall survival (OS) compared with pembrolizumab as first-line treatment for patients with stage III/IV non-small cell lung cancer (NSCLC)  and PD-L1 expression of ≥50%, prompting termination of the study for futility. 

“Although [immune-oncology] monotherapy can benefit subsets of patients, there is an unmet need to improve long-term outcomes,” stated Mark Socinski, MD, AdventHealth Cancer Institute, Orlando, Florida, and coauthors. “Therefore, combination [immune-oncology] therapy targeting multiple pathways is attractive in this patient population.”

In this double-blind trial, 662 eligible patients were randomized 5:5:2 to receive either 900 mg of ociperlimab plus 200 mg of tislelizumab (n = 287), 200 mg of pembrolizumab (n = 287), or 200 mg of tislelizumab (n = 88) once every 3 weeks. The primary end point was OS with ociperlimab plus tislelizumab vs pembrolizumab. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), duration of response, and safety.

At the prespecified interim analysis, median OS was 31.9 months in the ociperlimab plus tislelizumab arm and 29.4 months in the pembrolizumab arm, resulting in a stratified hazard ratio (HR) of 0.97. Median OS was 27.7 months in the tislelizumab arm. Because the trial was terminated for futility, efficacy analyses were considered descriptive.

Despite the absence of an OS benefit, numerical differences were observed for PFS and ORR. Median PFS was 14.3 months in the ociperlimab plus tislelizumab arm, 10.5 months in the pembrolizumab arm, and 16.6 months in the tislelizumab arm. Corresponding ORRs were 61%, 48.8%, and 55.7%, respectively. Median duration of response was 18.6 months in the ociperlimab plus tislelizumab arm and 28.3 months in the pembrolizumab arm. 

Treatment-related adverse events were reported in 84.3% of patients in the ociperlimab plus tislelizumab arm, 79.4% of patients in the pembrolizumab arm, and 79.3% of patients in the  tislelizumab arm. Grade ≥3 treatment-related adverse events were reported in 34.6% of patients, 20.2% of patients, and 27.6% of patients, respectively. Safety profiles were consistent with previous experience, with no new safety signals identified. 

“AdvanTIG-302 did not validate the preclinical findings of an additive or synergistic benefit when combining anti-PD-1 and anti-TIGIT therapies,” concluded Dr Socinski et al. “Future directions may include evaluating novel combinations that may improve outcomes in patients who do not respond to treatment with anti-PD-1/PD-L1 monotherapy or who relapse or develop resistance.”

Source:

Socinski MA, Reck M, Paz-Ares L, et al. AdvanTIG-302: Phase 3 study of ociperlimab (anti-TIGIT) + tislelizumab (anti-PD-1) versus pembrolizumab in untreated, locally advanced, unresectable, or metastatic non-small cell lung cancer with PD-L1 ≥50%. J Thorac Oncol. Published online: July 14, 2026. doi: 10.1016/j.jtho.2026.104089