NovaBridge's Ragistomig Shows Promise in Checkpoint Inhibitor-Resistant Cancers with New Q6W Dosing Schedule
核心洞察
NovaBridge Biosciences (搜索) announced that expanded Phase 1 data for ragistomig, a 4-1BB (搜索) X PD-L1 (搜索) bispecific antibody, will be presented at ESMO-IO 2025 on December 10th.
The study achieved its objective of extending the therapeutic window with a new every-six-week dosing schedule that produced strong anti-tumor efficacy in PD-L1 (搜索) non-responders while improving safety profile.
Ragistomig is designed to treat patients who are relapsed or refractory to checkpoint inhibitors, addressing resistance in a multi-billion dollar drug class.
NovaBridge Biosciences (搜索) announced that expanded Phase 1 data for ragistomig, a novel 4-1BB (搜索) X PD-L1 (搜索) bispecific antibody designed to overcome checkpoint inhibitor resistance, will be presented at the European Society for Medical Oncology – Immuno-Oncology Congress 2025 (ESMO-IO 2025). The poster presentation, scheduled for December 10th at 5:30 PM GMT, will showcase results from a dosing study that successfully extended the therapeutic window for this investigational cancer immunotherapy.
Extended Dosing Schedule Demonstrates Efficacy and Safety
The expanded Phase 1 dosing study achieved its primary objective of defining a new dosing schedule that balances efficacy with improved tolerability. According to Phillip Dennis, MD, PhD, Chief Medical Officer of NovaBridge, "The expanded Phase 1 dosing study achieved its objective of extending the therapeutic window for ragistomig by defining a new dosing schedule that could provide strong anti-tumor efficacy and a more manageable tolerability profile, including improved hepatic safety."
The new every-six-week (Q6W) extended dosing interval produced strong anti-tumor efficacy specifically in PD-L1 (搜索) non-responders, a patient population that represents a significant unmet medical need. The study results build upon promising Phase 1 data previously presented at the 2024 American Society for Clinical Oncology Annual Meeting (ASCO 2024).
Targeting Checkpoint Inhibitor Resistance
Ragistomig (also known as ABL503) addresses a critical challenge in oncology: resistance to checkpoint inhibitors. As Sean Fu, PhD, Chief Executive Officer of NovaBridge, explained, "Ragistomig was designed to deliver new therapeutic options for patients who have developed resistance or relapsed after treatment with checkpoint inhibitors, a multi-billion dollar drug class that serves as the cornerstone of care for many cancers."
The bispecific antibody integrates a single-chain, Fc-silent PD-L1 (搜索) segment as a tumor engager and a 4-1BB (搜索) segment as a conditional T cell activator. This design was developed using ABL Bio (搜索)'s "Grabody-T" bispecific antibody platform technology to overcome resistance to PD-(L)1 inhibition while stimulating 4-1BB activation only in the presence of PD-L1 expressing tumor cells, minimizing the risk of off-tumor toxicity.
Immunological Mechanisms and Clinical Development
The interim results to be presented at ESMO-IO include detailed immunological data demonstrating CD8+ cell proliferation and memory T-cell activation. The poster, titled "Phase 1 Clinical Trial of Ragistomig (ABL503/TJ-L14B: PD-L1 (搜索) × 4-1BB (搜索) bispecific antibody) Q6W Dosing Balances Favorable Safety and Sustained Efficacy Through Extended Immunologic Memory and Reinvigoration of CD8+ T Cells," will be presented by Gerald Falchook, MD, Director of the Sarah Cannon Research Institute (搜索) (SCRI) at HealthONE Denver.
Preclinical studies demonstrated that ragistomig showed superior anti-tumor activity compared to its single-agent components. The ongoing Phase 1 dose expansion study (NCT04762641) is being conducted in the United States and South Korea, with a primary endpoint of defining the dose-limiting toxicity and adverse event profile of ragistomig. Secondary endpoints include objective response rate, pharmacokinetic and immunogenicity profiles.
Partnership and Future Development
Ragistomig is being jointly developed by NovaBridge and ABL Bio (搜索), with the data supporting progression to combination studies that could significantly advance patient care. The improved safety profile, particularly the enhanced hepatic safety observed with the Q6W dosing schedule, positions ragistomig as a potentially important addition to the immunotherapy landscape for patients with checkpoint inhibitor-resistant cancers (搜索).
The presentation at ESMO-IO 2025 represents a key milestone in the development of ragistomig, providing the scientific community with comprehensive data on this novel bispecific antibody's potential to address the significant clinical challenge of checkpoint inhibitor resistance in cancer treatment.