Researchers across 79 centers in China reported that a combination regimen of programmed death-ligand 1 (PD-L1) inhibitor benmelstobart plus the multi-kinase inhibitor anlotinib produced statistically significant improvements in progression-free survival over pembrolizumab monotherapy in PD-L1-positive, driver gene-negative advanced non-small-cell lung cancer (NSCLC), according to the CAMPASS Phase III trial. The results were published in The Lancet Oncology. The trial, funded by Chia Tai Tianqing Pharmaceutical Group, enrolled 531 patients and represents one of the first randomized Phase III datasets to demonstrate head-to-head superiority over pembrolizumab in this setting. Chia Tai is responsible for discovering benmelstobart and development in Greater China, while US-based biotech Apollomics partnered with the China-based firm for rights outside China.
Pembrolizumab monotherapy has held a dominant position as first-line treatment for PD-L1-positive advanced NSCLC since its approval based on the KEYNOTE-024 and KEYNOTE-042 trials. However, a substantial proportion of patients progress within a year, and response rates in the broader PD-L1-positive population—defined as tumor proportion score (TPS) of 1% or greater—remain around 30% to 40%. The CAMPASS trial was designed to test whether adding anlotinib, a multi-target anti-angiogenic tyrosine kinase inhibitor, to the PD-L1-targeted benmelstobart could improve outcomes without the addition of chemotherapy.
The CAMPASS results
The trial randomized patients 2:1, with 354 receiving benmelstobart plus anlotinib and 177 receiving pembrolizumab plus placebo. Patients were aged 18 to 75 years, had an ECOG performance status of 0 or 1, and had no targetable EGFR or ALK mutations. Both squamous and non-squamous histologies were included. Enrollment ran from August 2021 through December 2022 across 79 sites in China.
The primary endpoint was progression-free survival assessed by blinded independent central review per RECIST v1.1. Median PFS in the experimental arm was not reached at the time of analysis, compared with 8.9 months in the pembrolizumab arm. The hazard ratio was 0.51 (95% CI: 0.39–0.67; p<0.0001). The 12-month PFS rate was approximately 60% with benmelstobart plus anlotinib versus approximately 40% with pembrolizumab. The PFS benefit was consistent across prespecified subgroups, including patients with TPS 1%–49% and ≥50%, as well as across squamous and non-squamous histologies.
Overall survival data, while still maturing with both medians not yet reached, showed a hazard ratio of 0.62 (95% CI: 0.44–0.88; p0.007), indicating an early OS signal in favor of the combination. The objective response rate was approximately 63% in the experimental arm versus 39% in the pembrolizumab arm, a statistically significant difference.
The mechanistic rationale for the combination centers on the relationship between tumor angiogenesis and immune suppression. Tumors upregulate VEGF signaling to promote vascular growth, but this process also creates an immunosuppressive microenvironment by reducing T-cell infiltration and promoting regulatory T-cell accumulation. Anlotinib inhibits VEGFR, FGFR, PDGFR, and c-Kit, which normalizes tumor vasculature and is thought to improve T-cell trafficking into the tumor. Benmelstobart then blocks the PD-1/PD-L1 axis, reactivating cytotoxic T-cells within a more accessible microenvironment. The hypothesis is that anti-angiogenic therapy potentiates checkpoint inhibition by making tumors more immunologically permissive, rather than relying on checkpoint blockade alone.