First-line benmelstobart–anlotinib combo yields PFS gain in advanced PD-L1-positive NSCLC

In the first-line treatment of patients with advanced PD-L1–positive non–small cell lung cancer (NSCLC), the combination of the anti-PD-L1 monoclonal antibody benmelstobart plus the multikinase inhibitor anlotinib prolongs progression-free survival (PFS) compared with pembrolizumab monotherapy, according to the phase III CAMPASS study conducted in China.

CAMPASS met its primary endpoint, and the median PFS—as assessed by independent review committee based on RECIST 1.1—was 11.0 months with the benmelstobart–anlotinib combination vs 7.1 months with pembrolizumab, with 6-month rates of 74.7 percent vs 56.8 percent, respectively, reported Dr Baohui Han from the Shanghai Chest Hospital in Shanghai, China. [ASCO 2025, abstract LBA8502]

Compared with pembrolizumab, the combination was associated with a 30-percent reduction in the risk of progression or death (hazard ratio [HR], 0.70, 95 percent confidence interval [CI], 0.54–0.90; p=0.0057), Han added.

In the prespecified subgroup analyses, the PFS benefit with benmelstobart–anlotinib combination was pronounced among patients with high PD-L1 expression (TPS ≥50 percent) (median, 13.3 vs 7.2 months; HR, 0.60, 95 percent CI, 0.41–0.88) and those with squamous NSCLC (median, 11.0 vs 6.9 months; HR, 0.63, 95 percent CI, 95 percent CI, 0.46–0.86).

Furthermore, patients in the combination arm showed more favourable tumour responses than those in the pembrolizumab arm, according to Han. The objective response rates in the respective arms were 57.3 percent vs 39.5 percent (odds ratio, 2.08, 95 percent CI, 1,43–3.01; p=0.001), and the disease control rates were 85.9 percent vs 79.1 percent (p=0.047).

As for safety, “combination treatment did not increase the incidence of permanent treatment discontinuation or death due to treatment-related adverse events (TRAEs) compared with pembrolizumab,” he said.

Grade ≥3 TRAEs occurred in 58.5 percent of patients in the combination arm and in 29.0 percent in the pembrolizumab arm. The most common were hypertension, palmar-plantar erythrodysesthesia syndrome, hypertriglyceridemia, asthenia, gamma-glutamyl transferase elevation, decreased platelet count, and anaemia.

The incidences of immune-related grade ≥3 TRAEs (10.8 percent vs 12.5 percent), treatment-related serious AEs (25.3 percent vs 21.0 percent), and TRAEs leading to any treatment discontinuation (7.1 percent vs 8.0 percent) or death (1.4 percent vs 2.3 percent) were comparable between the combination and pembrolizumab arms.

“To our knowledge, this is the first phase III study to demonstrate the significant PFS benefit of a multikinase inhibitor plus an anti-PD-L1 monoclonal antibody in the first-line treatment of advanced PD-L1-positive NSCLC compared with pembrolizumab,” Han said. “The findings support the combination as a potential option in the first-line treatment of [this population].”

Winning in lung cancer treatment

Study discussant Dr Ticiana Leal from the Emory University School of Medicine in Atlanta, Georgia, US, noted that CAMPASS was a well-designed phase III study of benmelstobart plus anlotinib with a positive primary endpoint of PFS. The combination has a manageable safety profile, with AEs consistent with VEGF inhibition.

This bears importance to the Chinese population with lung cancer, also because anlotinib is already an approved drug for NSCLC in later lines in China, Leal added.

However, Leal emphasized that pembrolizumab, which was the comparator arm, is not a standard of care for all PDL-1 levels. She also pointed out that there have been several negative studies investigating multi-targeted TKIs, including the frontline study LEAP 007 investigating lenvatinib plus pembrolizumab for patients with metastatic NSCLC and PD-L1 expression (TPS ≥1 percent).

“Unless overall survival benefit is documented, [benmelstobart plus anlotinib] is unlikely to be adopted for routine practice. [Furthermore,] biomarker development is needed to select patients for this treatment strategy,” Leal said.

“Getting right out of the gate first does not equate to finishing the race strong. In lung cancer, winning means good efficacy and good tolerability. The winning combination will not just be based on efficacy but based on having the best therapeutic index and predictive biomarker,” she concluded.

CAMPASS study

CAMPASS included 531 patients with locally advanced or recurrent/metastatic NSCLC with PD-L1 positive expression (TPS ≥1 percent), ECOG PS of 0–1, no EGFR mutations or ALK or ROS1 rearrangements, and had no prior exposure to antiangiogenic agents or immune checkpoint inhibitors.

The patients were randomly assigned to receive either benmelstobart 1,200 mg plus anlotinib 12 mg (n=354) or pembrolizumab 200 mg plus placebo (n=177). Anlotinib or placebo was taken orally daily on days 1–14 of a 21-day cycle, while benmelstobart or pembrolizumab was given intravenously on the first day of each cycle.

The median age of the population was 65 years, with most patients being male (84.7 percent) and former smokers (64.8 percent). The majority of patients had squamous NSCLC (60.3 percent), had stage IV disease at baseline (73.8 percent), had PD-L1 TPS 1–59 percent (55.0 percent). More patients in the combination group than in the pembrolizumab group had bone metastasis (25.7 percent vs 15.3 percent).

The median follow-up for PFS was 11.4 months for the combination arm and 10.6 months for the pembrolizumab arm.