Aptevo Therapeutics and Alligator Bioscience have announced positive preliminary data from their Phase 1 trial of ALG.APV-527, a first-in-class bispecific antibody targeting solid tumors. The trial met its primary endpoints, demonstrating adequate exposure, safety, tolerability, and biological activity. These findings suggest that ALG.APV-527 could offer a novel approach to cancer immunotherapy, particularly for patients with tumors expressing the 5T4 antigen.
The Phase 1 trial is a multi-center, multi-cohort, open-label dose-escalation study. Patients with various solid tumor types likely to express the 5T4 antigen were enrolled. ALG.APV-527 was administered intravenously once every two weeks, with the trial assessing safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity.
Clinical Activity and Safety
Among evaluable patients, 56% (9 out of 16) achieved stable disease. Notably, a colon cancer patient experienced stable disease for over six months, and a breast cancer patient remained stable for more than 11 months. A significant highlight was the absence of serious liver toxicity, a common side effect associated with other 4-1BB targeting treatments. This favorable safety profile could allow for longer treatment durations and improved real-world outcomes.
Dr. Thomas Marron, MD, PhD, Professor of Immunology & Immunotherapy and Hematology/Oncology at the Icahn School of Medicine at Mount Sinai, and a leading investigator in the trial, noted, "The interim results from Phase 1 trials of ALG.APV-527 are showing encouraging outcomes, particularly in terms of safety and disease stability in the trial patients who were refractory to multiple previous therapies... These findings underscore the drug's potential as a viable option for patients with solid tumors."
Biological Activity and Mechanism of Action
Biomarker analysis confirmed the biological activity of ALG.APV-527. Serum concentrations of the antibody were proportional to the administered dose. Furthermore, analysis of biomarkers in patient biopsies indicated immune activation in the tumor microenvironment, consistent with the drug's expected mechanism of action. ALG.APV-527 is designed to bind simultaneously to 4-1BB and 5T4, conditionally activating 4-1BB only in the presence of the 5T4 tumor-associated antigen. This approach aims to enhance anti-tumor immunity while minimizing systemic toxicities.
Potential Implications
The solid tumor market represents a substantial commercial opportunity, particularly in breast and colon cancer, based on the observed durability data. The absence of serious liver toxicity could be a key differentiator, potentially enabling longer treatment durations and better real-world outcomes compared to existing 4-1BB targeting approaches. These preliminary results suggest that ALG.APV-527 holds promise as a novel bispecific antibody for the treatment of solid tumors, warranting further investigation in larger clinical trials.
