Dr. Milhem on Design of Phase 1b/2 Study With AST-008 in CSCC

Mohammed M. Milhem, MBBS, Holden Chair of Experimental Therapeutics, associate director of clinical research at Holden Comprehensive Cancer Center; director of the Melanoma Program, chief of the Section of Oncology in the Department of Internal Medicine, and a clinical professor at the University of Iowa Hospital and Clinics, discusses the design of an open-label, multicenter phase 1b/2 dose escalation/expansion study with AST-008 in combination with a PD-1 inhibitor, such as pembrolizumab (Keytruda) or cemiplimab (Libtayo), in Merkel cell carcinoma and cutaneous squamous cell carcinoma (CSCC).

The phase 1b portion of this research was a dose-escalation study, says Milhem. Patients who were given AST-008 started off by receiving 2 mg of the molecule, which was injected directly into the tumor; this was combined with pembrolizumab. The dose for AST-008 escalated from 2 mg all the way up to 32 mg, adds Milhem. The safety data for that portion of the study were presented at several meetings and did not reveal any dose-limiting toxicities; patients tolerated this approach very well, according to Milhem. Patients with different tumor types, such sarcomas, melanomas, CSCC, and Merkel cell carcinoma tumors, were allowed to participate in the phase 1b dose-escalation trial.

In the trial, AST-008 was given by itself for the first 2 weeks, which helped to define its dose-limiting toxicity. The molecule was then combined with an anti–PD-1 agent, either pembrolizumab or cemiplimab, for another 3 weeks; that was another way to define the dose-limiting toxicity. If no dose-limiting toxicities were reported in both of those 2 periods, the next dose escalation was identified. The final dose that was accepted into the phase 2 portion of this study was 32 mg, notes Milhem.

Two cohorts were selected for exceptional responses: those with Merkel cell carcinoma and those with CSCC. The phase 2 trial further examining the approach in these subgroups is currently ongoing. Investigators plan to enroll 10 patients first to see whether they develop a partial or complete response to the treatment. If they do, then enrollment will be expanded to a total of 29 patients in each of those 2 cohorts, concludes Milhem.