Editor’s Note: Since the PACIFIC trial established sequential immunotherapy following chemoradiotherapy as the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC), improving upon this strategy has become a global priority. At the 2025 ASCO Annual Meeting, the R-ALPS study (Abstract #LBA8004), led by Dr. Ming Chen and his team at Sun Yat-sen University Cancer Center, was selected as a Late-Breaking Abstract (LBA), generating significant interest and discussion. This phase III clinical trial was the first to explore a dual-maintenance approach using the domestic PD-L1 inhibitor bemusuzutamide (TQB2450) in combination with the anti-angiogenic agent anlotinib. The median progression-free survival (PFS) reached 15.1 months, outperforming both the monotherapy arm (9.7 months) and the placebo arm (4.2 months). Oncology Frontier invited Dr. Ming Chen to share an in-depth interpretation of the trial results and their clinical significance.Study Overview
The R-ALPS study was a randomized, double-blind, placebo-controlled, multicenter phase III clinical trial (Abstract #LBA8004) evaluating the use of TQB2450 with or without anlotinib as maintenance therapy in patients with unresectable stage III NSCLC who did not experience disease progression after concurrent or sequential chemoradiotherapy.
TQB2450 (bemusuzutamide) is a novel humanized IgG1 monoclonal antibody targeting programmed death-ligand 1 (PD-L1). Anlotinib is a multi-target anti-angiogenic tyrosine kinase inhibitor (TKI) that has shown synergistic effects with PD-(L)1 inhibitors by promoting tumor vessel normalization and enhancing T-cell infiltration, thus improving antitumor immunity in advanced NSCLC.
In the phase III R-ALPS study (NCT04325763), 553 patients with unresectable stage III NSCLC who had no disease progression after concurrent or sequential chemoradiotherapy (60 Gy ±10%) were randomly assigned to three arms: TQB2450 (1200 mg, intravenous, every three weeks) combined with anlotinib (8 mg, oral, days 1–14 every three weeks); TQB2450 monotherapy; and placebo. The first stage of randomization used a 1:1:1 ratio, followed by a 1:1 allocation in the second stage. Stratification factors included smoking history (yes/no) and prior chemoradiotherapy modality (sequential or concurrent). The primary endpoint was progression-free survival (PFS) as assessed by an independent review committee (IRC) using RECIST v1.1 criteria.
Results (Data cut-off: November 30, 2023)
The median PFS (mPFS) by IRC was 15.1 months (95% CI: 9.4 to 21.7) in the combination group, significantly longer than 4.2 months in the placebo group, with a hazard ratio (HR) of 0.49 (95% CI: 0.36 to 0.66; P < 0.0001). In the monotherapy group, the mPFS was 9.7 months (95% CI: 6.0 to 34.4), also significantly better than placebo, with an HR of 0.53 (95% CI: 0.39 to 0.72; log-rank P < 0.0001).
The 12-month PFS rates were 54.9% in the combination group, 45.7% in the monotherapy group, and 26.4% in the placebo group.
Overall survival (OS) data remained immature at the time of the interim analysis and are expected to be updated in future follow-ups.
In terms of safety, the incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was 49.8% in the combination group, 31.8% in the monotherapy group, and 21.2% in the placebo group. The most commonly reported adverse events were hypertension (8.6%, 1.0%, and 1.5% respectively) and hypertriglyceridemia (9.6%, 2.8%, and 1.5% respectively). The proportions of patients who discontinued treatment due to TEAEs were 22.5% in the combination arm, 14.2% in the monotherapy arm, and 9.1% in the placebo arm.
Results (Data cut-off: July 8, 2024)
The IRC-assessed median PFS was 17.4 months (95% CI: 12.5 to 24.8) in the combination arm and 11.2 months (95% CI: 7.0 to 20.7) in the monotherapy arm, with a hazard ratio of 0.82 (95% CI: 0.63 to 1.08; log-rank P = 0.1218).
Conclusion
Compared with placebo, both TQB2450 monotherapy and its combination with anlotinib significantly prolonged PFS in patients with unresectable stage III NSCLC. Secondary endpoints also favored the treatment arms, and the safety profile remained within an acceptable range. These findings support the dual-maintenance strategy as a viable and innovative “China solution” in the post-chemoradiotherapy setting for stage III NSCLC.
Researcher’s Perspective
Oncology Frontier: First of all, congratulations on the release of this Late-Breaking Abstract. The R-ALPS study explored the dual-maintenance strategy of TQB2450 combined with anlotinib in patients with locally advanced, unresectable NSCLC. What key clinical challenges does this study aim to address?
Dr. Ming Chen: Among patients with NSCLC, approximately one-third are diagnosed at a stage where complete surgical resection is not feasible, yet distant metastasis has not occurred. This group is referred to as having unresectable, locally advanced NSCLC. The current standard of care involves maintenance therapy with a PD-L1 inhibitor following completion of chemoradiotherapy. Building on this standard, our study sought to answer two key questions: first, whether the domestically developed PD-L1 inhibitor bemusuzutamide (TQB2450) delivers efficacy comparable to other international and domestic agents; and second, whether combining TQB2450 with the anti-angiogenic agent anlotinib can establish a novel dual-maintenance treatment model that improves upon existing monotherapy strategies.
In this study, we enrolled 553 patients with unresectable, stage III locally advanced NSCLC. The data showed that the trial met its primary endpoint, as assessed by the Independent Review Committee (IRC): TQB2450 monotherapy maintenance significantly outperformed placebo, while the combination of TQB2450 and anlotinib further improved outcomes over both placebo and monotherapy. Therefore, both of the study’s core objectives have been essentially fulfilled.
Oncology Frontier: What survival outcomes were observed with TQB2450 monotherapy and TQB2450 plus anlotinib in terms of the primary efficacy endpoint?
Dr. Ming Chen: Specifically, the median PFS for the TQB2450 monotherapy group reached 9.7 months, clearly surpassing the 4.2 months observed in the placebo arm. The dual-maintenance regimen of TQB2450 combined with anlotinib achieved even more favorable results, with median PFS extended to 15.1 months. These findings indicate that the dual-maintenance strategy delivered the greatest efficacy, followed by monotherapy, with both demonstrating a clear benefit over placebo.
Oncology Frontier: What is the theoretical rationale behind combining TQB2450 and anlotinib as a maintenance therapy? How does this combination synergistically enhance the immune microenvironment post-chemoradiotherapy?
Dr. Ming Chen: Anti-angiogenic therapy works by inhibiting tumor angiogenesis, thereby suppressing tumor growth and metastasis. It can induce a temporary window of vascular normalization during which drug perfusion is improved. This enhances T-cell infiltration, boosts the efficacy of immunotherapy, and helps remodel the tumor immune microenvironment. This laboratory finding forms the theoretical foundation for why a dual-maintenance strategy using anlotinib combined with a PD-L1 inhibitor may outperform monotherapy. That said, it is important to acknowledge that the incidence of adverse events was higher in the dual-therapy group compared to monotherapy.
Oncology Frontier: Based on the findings of the R-ALPS study, do you believe the TQB2450 plus anlotinib regimen could become a new standard of care? Compared to the current standard, what would you consider to be its main advantages?
Dr. Ming Chen: When compared with data from the PACIFIC model and other similar studies, the dual-maintenance regimen demonstrated a slight efficacy advantage in our trial, while maintaining a comparable safety profile. Based on these results, we are optimistic about the potential for this regimen to be approved as a new therapeutic option, providing patients with an additional line of treatment.
Reference: Ming Chen, Yongling Ji, Long Chen, et al. R-ALPS: A randomized, double-blind, placebo-controlled, multicenter phase III clinical trial of TQB2450 with or without anlotinib as maintenance treatment in patients with locally advanced and unresectable (stage III) NSCLC without progression following concurrent or sequential chemoradiotherapy. ASCO 2025; Abstract LBA8004.
Dr. Ming Chen
Sun Yat-sen University Cancer Center
Director, Department of Radiation Oncology, Sun Yat-sen University Cancer Hospital Chief Lung Cancer Specialist, Sun Yat-sen University Cancer Hospital Director, Advanced Radiation Technology Laboratory, Sun Yat-sen University Chair, Radiotherapy Expert Committee, Chinese Society of Clinical Oncology (CSCO) Chair, Particle Therapy Committee, Chinese Anti-Cancer Association Vice Chair, Radiation Oncology Branch, Chinese Medical Association
