NAYA Biosciences has announced the initiation of a Phase 1/2a clinical trial to evaluate NY-303, a GPC3-targeting NK Engager bispecific antibody, for the treatment of hepatocellular carcinoma (HCC) in patients who have not responded to first-line immunotherapy. The trial, which has received regulatory approval from the Israeli Ministry of Health and institutional review board clearance, will enroll patients at up to seven academic centers, with patient recruitment expected to begin in early 2025.
Trial Design and Endpoints
The Phase 1 portion of the trial will involve dose escalation, with responding patients continuing weekly administration as long as no disease progression is observed. Key endpoints include safety, pharmacokinetics, activity markers, preliminary clinical efficacy, and time-to-progression. The Phase 2a part of the trial is anticipated to expand to the United States and Europe, pending regulatory approvals, and will evaluate NY-303 at two dose levels selected in Phase 1. Key efficacy endpoints for Phase 2a will include objective response rate and progression-free survival.
Rationale for NY-303 in HCC
Hepatocellular carcinoma is a leading cause of cancer death worldwide, with a rapidly increasing global trend. According to NAYA Therapeutics Chief Medical Officer Dan Chiche, MD, less than 30% of patients treated with current standard of care respond to immunotherapy, and mean progression-free survival is less than 7 months. NY-303's dual targeting of NK cells and GPC3 represents a novel mechanism of action with the potential to unlock non-response to checkpoint inhibitors.
NY-303 Mechanism of Action
NY-303 is a first-in-class therapeutic candidate that leverages the engagement and activation of natural killer (NK) cells using a bispecific antibody. It targets both GPC3, an oncofetal protein uniquely expressed on liver cancer cells, and NKp46, a cell surface receptor on natural killer (NK) cells that plays a central role in NK cell activation and the elimination of target cells. This mechanism enables NY-303 to turn the tumor from a 'cold' state into a 'hot' state, making liver cancer cells susceptible to immunotherapy. The approach is promising not only for HCC but also for other GPC3-expressing tumors like lung squamous cell carcinoma, ovarian cancer, and pediatric cancer.
Current HCC Treatment Landscape
Currently, liver cancer therapies include surgery, liver transplantation, targeted drugs, and immunotherapies like checkpoint inhibitors. However, the prognosis remains grim, especially for advanced-stage disease, with a global five-year survival rate of around 20%. NY-303 represents a new opportunity for liver cancer patients by harnessing the body’s immune system to specifically attack tumor cells and engage NK-cells, potentially offering a safer profile and overcoming non-responding tumors against immunotherapies.
