Clinical Summary:

• Design/Population: The phase 3 TQB2450-III-11 trial randomized previously untreated patients with locally advanced or metastatic EGFR/ALK/ROS1–wild-type non-squamous NSCLC to receive either benmelstobart plus platinum-pemetrexed followed by benmelstobart/anlotinib/pemetrexed maintenance or tislelizumab plus platinum-pemetrexed followed by tislelizumab/pemetrexed maintenance.
• Key Outcomes: Benmelstobart-based therapy significantly improved progression-free survival compared with the tislelizumab-based regimen, with benefit observed across most patient subgroups.
• Clinical Relevance: Benmelstobart plus chemotherapy followed by anlotinib-containing maintenance may provide a new first-line option for advanced non-squamous non-small cell lung cancer, particularly by extending progression-free survival beyond a PD-1-chemotherapy comparator while maintaining a manageable safety profile.

Results from the phase 3 TQB2450-III-11 trial demonstrated that benmelstobart plus chemotherapy followed by maintenance benmelstobart, anlotinib, and pemetrexed significantly improved progression-free survival (PFS) compared with a tislelizumab-based regimen among patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).

These results were presented by Yuankai Shil, MD, Peking Union Medical College, Beijing, China, at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this open-label study, 596 patients with EGFR/ALK/ROS1-wild type non-squamous NSCLC were randomized 1:1 to receive either 1200 mg of benmelstobart or 200 mg of tislelizumab once every 3 weeks plus 4 cycles of platinum-pemetrexed chemotherapy and pemetrexed. Maintenance consisted of 4 cycles of either benmelstobart plus 10 mg of anlotinib and pemetrexed or tislelizumab plus pemetrexed, administered until disease progression or unacceptable toxicity. Patients were stratified by PD-L1 score and prior systemic therapies. The primary end point was PFS. 

At analysis, median PFS was 14.42 months in the benmelstobart arm and 8.34 months in the tislelizumab arm (hazard ratio [HR], 0.67; 95% [CI], 0.52 to 0.86; P = .0017). Subgroup analyses demonstrated consistent benefit across most patient groups, with particularly notable improvements among patients with ECOG performance status 0 (HR, 0.36; 95% CI, 0.20 to 0.65) and those with PD-L1 tumor performance status of <1% (HR, 0.61; 95% CI, 0.43 to 0.86). OS results were immature at analysis.

Any grade Treatment-emergent adverse events were reported in 92.28% of patients in the benmelstobart arm and 90.94% of patients in the tislelizumab arm. Grade ≥3 treatment-related adverse events were reported in 56.38% and 48.66% of patients, respectively. Immune-related adverse events were reported in 19.13% of patients in the benmelstobart arm and 18.46% in the tislelizumab arm.

“Benmelstobart in combination with chemotherapy followed by sequential combination with anlotinib significantly improved PFS compared to tislelizumab in combination with chemotherapy followed by sequential tislelizumab, with a manageable safety profile,” concluded Dr Shil. “It might be a new first-line treatment for [non-squamous] NSCLC.”

Source:

Shi Y, Tang X, Wu L, et al. A randomized, open-label, parallel-controlled phase 3 trial of benmelstobart plus chemotherapy and anlotinib for first-line treatment of advanced non-squamous non–small cell lung cancer. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA8507.