NEW YORK – Alentis Therapeutics on Thursday said it began a Phase I/II trial of its Claudin-1 (CLDN1)-targeted antibody ALE.C04 in patients with CLDN1-positive head and neck tumors.
In the trial, researchers will study ALE.C04 alone and in combination with Merck's anti-PD-1 antibody Keytruda (pembrolizumab) in 220 patients with recurrent or metastatic head and neck squamous cell carcinoma. In Phase I, Alentis will test three doses of ALE.C04 as a monotherapy and ALE.C04-Keytruda at two dose levels. The trial will also include a dose-expansion portion to gauge ALE.C04's anti-tumor activity as a single agent and establish the recommended Phase II dose for ALE.C04 when given with Keytruda. In Phase II, investigators will determine a recommended Phase II dose for ALE.C04 as a monotherapy and compare ALE.C04-Keytruda to Keytruda alone at the recommend Phase II dose.
The company will measure dose-limiting toxicities, objective response rate, and progression-free survival in the study. As additional secondary outcome measures, researchers will track patients' disease control rate, duration of response, overall survival, and other efficacy measures, as well as immunogenicity and pharmacokinetics.
ALE.C04 is designed to remodel the tumor microenvironment by binding to CLDN1, which is expressed on the surface of cancer cells. Basel, Switzerland-based Alentis is expecting the resulting changes will allow T-cell infiltration into tumors and fibrotic organs and cause tumor death.
"ALE.C04 is designed to kill CLDN1-positive tumor cells directly and to break the checkpoint inhibitor treatment resistance by restoring immune cell trafficking," Alentis Chief Medical Officer Luigi Manenti said in a statement.