Aptevo Therapeutics has reported encouraging results from its Phase 1 dose escalation study of ALG.APV-527, a novel bispecific antibody designed to target solid tumors. The trial, evaluating multiple solid tumor types expressing the 5T4 antigen, has demonstrated promising efficacy and safety outcomes.
In a significant development for patients with limited treatment options, 10 out of 17 efficacy evaluable patients (59%) achieved stable disease. Notably, a breast cancer patient who entered the study with progressive disease maintained stable disease for over 12 months and successfully transitioned to higher dose levels twice. Additional durability was observed in a colon cancer patient who maintained stable disease for more than six months, while a prostate cancer patient has remained stable for at least four months.
The drug's safety profile has emerged as a key differentiator. ALG.APV-527 demonstrated limited incidence of liver toxicity, with no severe cases reported – a significant advantage over similar treatments where hepatotoxicity often becomes dose-limiting.
Dr. Dirk Huebner, Chief Medical Officer at Aptevo, emphasized the potential impact of these findings: "ALG.APV-527 treatment was not associated with serious liver toxicities, which can be treatment limiting and are commonly seen in similar drugs. We believe this safety feature could provide significant differentiation among competitors."
Mechanism of Action and Target Population
ALG.APV-527 operates as a bispecific conditional 4-1BB agonist, becoming active only upon simultaneous binding to both 4-1BB and 5T4. This dual-targeting approach stimulates immune cells involved in tumor control, specifically antitumor-specific T cells and NK cells, while targeting 5T4, an oncofetal tumor-associated antigen.
The drug's potential reach extends across multiple cancer types, including:
- Non-small-cell lung carcinoma (NSCLC)
- Breast cancer
- Head and neck cancer
- Cervical cancer
- Renal cancer
- Gastric cancer
- Colorectal cancer
Trial Design and Administration
The Phase 1 trial employed a multi-center, multi-cohort, open-label dose-escalation design, administering ALG.APV-527 across up to six escalating dose levels. The treatment schedule involves intravenous administration every two weeks, with the study assessing safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity.
Development Partnership
ALG.APV-527 is being developed in partnership with Alligator Bioscience, combining both companies' expertise in immunotherapy development. The collaboration aims to address significant unmet needs in solid tumor treatment, particularly in patient populations where current therapeutic options are limited.
The results were presented at both the European Society for Medical Oncology Congress and the Society for Immunotherapy of Cancer Conference in 2024, highlighting the scientific community's interest in this novel therapeutic approach.
