NAYA Biosciences Initiates Phase 1/2a Trial of NY-303 for Hepatocellular Carcinoma
核心洞察
NAYA Biosciences (搜索) has commenced a Phase 1/2a clinical trial for NY-303, a GPC3 (搜索)-targeting NK Engager bispecific antibody, in patients with hepatocellular carcinoma (搜索) (HCC (搜索)).
The trial will assess the safety and efficacy of NY-303 as a monotherapy in patients who have not responded to first-line immunotherapy.
Phase 1 will focus on dose escalation, while Phase 2a will expand to the US and Europe to evaluate objective response rate and progression-free survival.
NAYA Biosciences (搜索) has announced the initiation of a Phase 1/2a clinical trial for NY-303, a GPC3 (搜索)-targeting NK Engager bispecific antibody, in patients with hepatocellular carcinoma (搜索) (HCC (搜索)) who have not responded to first-line immunotherapy. The trial, approved by the Israeli Ministry of Health and institutional review boards, will evaluate the safety and efficacy of NY-303 as a monotherapy. Patient recruitment is planned for early 2025 at leading medical centers in Israel, including Hadassah Hospital, Sheba Medical Center, and Sourasky Medical Center.
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 (搜索) is a significant global health challenge, with over 900,000 new cases annually and a rising incidence in the United States. Current standard of care, including immunotherapy, has limited efficacy, with less than 30% of patients responding and a mean progression-free survival of less than 7 months. NY-303 offers a novel mechanism of action by dually targeting NK cells and GPC3 (搜索), potentially unlocking non-response to checkpoint inhibitors.
NY-303 Mechanism of Action
NY-303 is a first-in-class therapeutic candidate that engages and activates natural killer (NK) cells using a bispecific antibody. It targets both GPC3 (搜索), an oncofetal protein uniquely expressed on liver cancer cells, and NKp46, a cell surface receptor on NK cells that plays a central role in NK cell activation and the elimination of target cells. This mechanism enables NY-303 to transform the tumor microenvironment from "cold" to "hot," making liver cancer cells susceptible to immunotherapy. This approach is particularly promising for HCC (搜索) patients who face limited treatment options and poor survival rates, as well as for other GPC3-expressing tumors like lung squamous cell carcinoma (搜索), ovarian cancer (搜索), and pediatric cancers.
Current HCC Treatment Landscape
Existing liver cancer therapies include surgery, liver transplantation, targeted drugs, and immunotherapies like checkpoint inhibitors. However, the prognosis remains poor, especially for advanced-stage disease, with a global five-year survival rate of around 20%. NY-303 represents a new opportunity by harnessing the body’s immune system to specifically attack tumor cells and engage NK-cells, offering potent anti-cancer effects with a potentially safer profile compared to traditional treatments. It aims to reduce side effects often associated with chemotherapy and overcome non-responding tumors against immunotherapies.