NEW YORK – Actinium Pharmaceuticals on Tuesday said it will evaluate whether its radiotherapeutic Actimab-A can boost the efficacy of PD-1 inhibitors in PD-L1-expressing solid tumors in a new clinical program.
Actinium researchers will compare Actimab-A plus Merck's Keytruda (pembrolizumab) against Keytruda alone and Actimab-A plus Bristol Myers Squibb's Opdivo (nivolumab) against Opdivo alone in two separate trials involving patients with head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC). Actinium will enroll patients with locally advanced HNSCC or NSCLC whose tumors express PD-L1. The researchers will track measures of safety and efficacy, including overall response rate, progression-free survival, and overall survival. They will also explore biomarkers, including the pattern of depletion of CD33-positive myeloid derived suppressor cells (MDSCs) and T-cell activity in peripheral blood.
Studies in the scientific literature suggest that the efficacy of PD-1 inhibitors is limited by the accumulation of MDSCs in the tumor microenvironment. Actimab-A is a radiotherapeutic designed to target the CD33 antigen, which is expressed on the surface of MDSCs, and to deliver the alpha particle-emitting radioisotope actinium-225. Based on preclinical studies, the New York-based company believes that depletion of MDSCs by Actimab-A could be an effective strategy to improve outcomes with PD-1 inhibitors. The firm expects to report proof-of-concept data from the first of these trials in the second half of 2025.
"The Actimab-A solid tumor program … has the potential to address the high unmet need of patients receiving PD-1 checkpoint inhibitors whose cancer stops responding or progresses," Actinium Chief Medical Officer Avinash Desai said in a statement. "Our preclinical data is highly encouraging, and we believe this novel approach combining Actimab-A with PD-1 inhibitors has immense potential."
In February 2023, Actinium signed a cooperative research and development agreement with the National Cancer Institute, under which it is providing Actimab-A for NCI-funded studies of the radiotherapy by itself and in combination with other agents. The studies currently under way by the Experimental Therapeutics Clinical Trials Network and National Clinical Trials Network include a registrational study of Actimab-A in combination with chemotherapy expected to begin this year, according to Actinium.