Anlotinib Following Benmelstobart Plus Chemotherapy Improves Progression-Free Survival in S-NSCLC

Benmelstobart (TQB2450; Chia Tai Tianqing Pharmaceutical Group Co, Ltd) in combination with chemotherapy followed by sequential combination with anlotinib (Catequentinib; Advenchen Laboratories) led to significant improvements in progression-free survival (PFS), with a manageable safety profile. The data, presented at the 2025 American Society of Clinical oncology Annual Meeting, suggest the regimen as a new first-line treatment for patients with squamous non-small cell lung cancer (s-NSCLC).

Visualization of lungs with tumors | Image Credit: © Alexej - stock.adobe.com

The standard first-line therapy for locally advanced or metastatic sq-NSCLC is PD-1/PD-L1 inhibitors plus platinum-based chemotherapy. However, the clinical benefit of the use of immune checkpoint inhibitors (ICIs) and antiangiogenic agents for patients remains uncertain, highlighting an urgent need to develop new therapeutic strategies. Studies indicate that anti-angiogenesis can augment the efficacy of ICIs across various cancer types. The normalization of blood vessels using antiangiogenic agents may promote immune cell infiltration and change the tumor microenvironment.^1,2

Anlotinib is a multitargeted anti-angiogenic agent that has shown a potential synergistic effect with ICI therapy, such as benmelstobart—a humanized anti-PD-L1 antibody. In the multicenter, randomized, double-blind, parallel-controlled phase 3 TQB2450-III-12 trial (NCT04234607), investigators evaluated benmelstobart in combination with chemotherapy followed by sequential combination with anlotinib compared with tislelizumab (Tevimbra; BeiGene) plus chemotherapy as first-line therapy for locally advanced or metastatic sq-NSCLC.^2,3

The investigators randomly assigned 565 patients to 1 of 2 groups. Group A was treated with benmelstobart (1200 mg, Q3W) plus chemotherapy for 4 cycles followed by benmelstobart plus anlotinib (10mg, PO, D1-D14, Q3W), and group B received tislelizumab (200mg, Q3W) plus chemotherapy for 4 cycles followed by tislelizumab. The patients were also treated with paclitaxel (175 mg/m², day 1) and carboplatin (area under the concentration [AUC] of 5, day 1) every 3 weeks.¹

The primary end point was PFS per RECIST 1.1 by independent review committee, with a key secondary end point of overall survival (OS).¹

Median PFS was superior in group A at about 10.12 months (95% CI, 8.54–NE) compared with 7.79 months in group B (95% CI, 6.87–9.69; hazard ratio [HR] = 0.64 [98.35% CI, 0.45–0.93; P = .0038]). In the subgroup analysis, PFS benefit favored group A in almost all subgroups, especially for patients with ECOG PS 0 (HR 0.44, 0.23–0.84), PD-L1 expression of 1% to 49% (HR 0.47, 0.30–0.73), and those 65 years and younger (HR 0.59, 0.39–0.90).¹

The ORR of group A was also superior at 71.9% versus 65.1% in group B, with durations of responses of 9.69 months (95% CI, 8.44–NE) and 8.34 months (95% CI, 5.78–NE), respectively. At the time of this interim analysis, the OS is immature.¹

Grade 3 or higher adverse events (AEs) related to benmelstobart, tislelizumab, or anlotinib/placebo occurred in approximately 61.57% of patients in group A and 51.06% in group B. The incidence of grade 5 treatment-emergent AEs (TEAEs) was similar between the groups, reported in 5.69% of group A and 5.63% of group B. Discontinuation of any treatment component because of TEAEs occurred in 4.27% of patients in group A and 5.28% in group B.¹

Benmelstobart combined with chemotherapy, followed by sequential treatment with anlotinib, significantly improved PFS and maintained a manageable safety profile. These findings suggest it may represent a promising new first-line treatment option for patients with sq-NSCLC.

REFERENCES

1. Shi Y, Sun L, Yang R, et al. Phase 3 study of benmelstobart in combination with chemotherapy followed by sequential combination with anlotinib for the first-line treatment of locally advanced or metastatic squamous non-small cell lung cancer (sq-NSCLC). 2025 ASCO Annual Meeting. May 30, 2025, to June 3, 2025. Chicago, IL. Abstract 8514.

2. Cheng Y, Chen J, Zhang W, et al. Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial. Nature Medicine. July 11, 2024. Doi:10.1038/s41591-024-03132-1

3. A study of TQB2450 or placebo combined with anlotinib, etoposide and carboplatin versus etoposide and carboplatin in subjects with extensive small cell lung cancer (ETER701). Updated January 22, 2020. Accessed June 25, 2025. https://clinicaltrials.gov/study/NCT04234607?term=NCT04234607&rank=1