Alligator Bioscience AB and Aptevo Therapeutics announced positive interim data from the dose escalation phase of their Phase 1 trial evaluating ALG.APV-527 for the treatment of solid tumors likely to express the tumor antigen 5T4. The multi-center, dose escalation trial is now more than 50% enrolled, and preliminary results include: Treatment was overall well-tolerated, and a maximum tolerated dose has not yet been determined, dose-escalation in higher-dose cohorts is ongoing, ALG.APV-527 could be measured in all patients with plasma concentration of ALG.APV-527 consistent with the administered dose, Biomarker analyses indicate the expression of the targets (4-1BB and 5T4) in tumor biopsies and confirm biological activity of ALG.APV-527. Of particular interest, signs of clinical activity were observed for both enrolled patients with heavily pre-treated breast cancer.

These patients demonstrated measurable level of drug in circulation (pharmacokinetic) and reproducible elevation of serum pharmacodynamic markers with dosing, suggesting the drug is biologically active. One patient remained on study for seven months and a second remains on study beyond nine months. Both patients achieved best overall response of stable disease.

The ALG.APV-527 Phase 1 trial is a multi-center, multi-cohort, open-label trial that will include six cohorts (dose levels) in a 3+3 design. The trial will be conducted at up to 10 sites in the U.S. among adult patients with multiple solid tumor types/histologies likely to express the 5T4 antigen. ALG.APV-527 will be given intravenously once every two weeks.

The trial will assess the safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ALG.APV-527. ALG.APV-527 is a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4. This has the potential to be clinically important because 4-1BB can stimulate the immune cells (antitumor-specific T cells and NK cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy.

5T4 is an oncofetal tumor associated antigen overexpressed on numerous solid tumors including non-small-cell lung carcinoma (NSCLC), breast, head and neck, cervical, renal, gastric, and colorectal cancer.