ArticleJournal for immunotherapy of cancer2025
Acasunlimab, an Fc-inert PD-L1×4-1BB bispecific antibody, combined with PD-1 blockade potentiates antitumor immunity via complementary immune modulatory effects.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 11 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 2, Multicenter, Randomized, Open-Label Trial of GEN1046 as Monotherapy and in Combination Pembrolizumab Therapy in Subjects With Relapsed/Refractory Metastatic Non-Small Cell Lung Cancer After Treatment With Standard of Care Therapy With an Immune Checkpoint Inhibitor
A Prospective, Open-Label, Randomized, Phase 3 Trial of Acasunlimab (GEN1046) in Combination With Pembrolizumab Versus Docetaxel in Subjects With PD-L1 Positive Metastatic Non-Small Cell Lung Cancer After Treatment With a PD-1/PD-L1 Inhibitor and Platinum-Containing Chemotherapy (ABBIL1TY NSCLC-06)
Who cites it
11 citing papers in PubMed.
- Review
- A phase 1 dose-finding and pharmacokinetic study of acasunlimab alone or in combination with pembrolizumab in Japanese patients with advanced or metastatic solid tumors.International journal of clinical oncology · 2026Article
- Apigenin 7-glucoside reprograms tumor metabolism and enhances immunotherapy efficacy in colorectal cancer via DLX5.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Review
- T-Cell Immunity and Lung Cancer.Respirology (Carlton, Vic.) · 2026Review
- Immune Exhaustion in Chronic Infection and Cancer: Signaling Pathways and Therapeutic Interventions.MedComm · 2026Review
- Phase 1 Study of INBRX-105, a TNFRSF9 (4-1BB) and PD-L1 Bispecific Antibody, in Patients with Select Solid Tumors.Cancer research communications · 2026Article
- Late-phase strategies to overcome limitations of PD-1/PD-L1 therapy: a clinical development trajectory through 2030.Frontiers in oncology · 2026Review
- The science of tumor-infiltrating lymphocytes (TIL): perspectives from the SITC Surgery Committee.Journal for immunotherapy of cancer · 2025Review
- Beyond monoclonal antibodies: constraints and the case for alternative PD-1/PD-L1-targeting formats.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNext-generation cancer immunotherapies aim to improve patient outcomes by combining inhibitory signal blockade with targeted T-cell costimulation in tumor and lymphoid tissues. Acasunlimab (DuoBody-PD-L1×4-1BB) is an investigational, bispecific antibody designed to elicit an antitumor immune response via conditional 4-1BB activation strictly dependent on simultaneous programmed death-ligand 1 (PD-L1) binding. Since 4-1BB is coexpressed with programmed cell death protein-1 (PD-1) on CD8
methodsThe effect of acasunlimab and pembrolizumab combination was analyzed in vitro using functional immune cell assays, including mixed-lymphocyte reactions and antigen-specific T-cell proliferation and cytotoxicity assays. The antitumor activity of the combination was tested in vivo in (1) MC38, MB49, Pan02, and B16F10 syngeneic tumor models using acasunlimab and anti-PD-1 mouse-surrogate antibodies; and (2) triple knock-in mice expressing the human targets using an acasunlimab chimeric antibody (chi-acasunlimab) and pembrolizumab. The mechanism of action of the combination was investigated in the MC38 syngeneic model through immunohistochemistry, flow cytometry, and bulk RNA sequencing.
resultsThe combination reinvigorated dysfunctional T cells in vitro, while also potentiating T-cell expansion, interleukin (IL)-2 and interferon gamma secretion and cytotoxic activity. In vivo, the combination of chi-acasunlimab and pembrolizumab or mouse-surrogate antibodies potentiated antitumor activity and survival in the humanized knock-in and multiple syngeneic mouse models, leading to durable complete tumor regressions in the MC38 model consistent with therapeutic synergy. Mechanistically, the combination enhanced clonal expansion of tumor-specific CD8
conclusionThese preclinical results demonstrate that conditional 4-1BB stimulation combined with complete PD-1 blockade enhances antitumor immunity through complementary mechanisms. The acasunlimab and pembrolizumab combination is being evaluated in Phase 2 (NCT05117242) and pivotal Phase 3 (NCT06635824) trials in patients with metastatic non-small cell lung cancer after checkpoint inhibitor therapy failure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.