A phase 1, multicenter, open-label, dose-escalation, combination study of RM-1929 and photoimmunotherapy in patients with recurrent head and neck cancer

Background: Patients with recurrent head and neck squamous cell cancer (rHNSCC) have a poor prognosis once they have failed definitive treatment. We have completed a Phase 1 dose-escalation study of a unique targeted light activated drug conjugate RM1929 consisting of the EGFR-directed monoclonal antibody cetuximab conjugated to the phthalocyanine dye IRDye 700DX. Methods: This was a Phase I study of rHNSCC patients who could not be satisfactorily treated with surgery, radiation, or platinum chemotherapy. The study included a drug dose-escalation with a fixed fluence light application to determine the drug dose that could be safely given to activate the pharmacodynamics of anticancer responses. Twenty-four hours after drug infusion non-thermal red light was applied to the tumors either on the surface for mucosal/skin disease or within the tumor via fiber optic diffusers for submucosal or nodal disease. Primary safety endpoints were assessed at 1 week and secondary efficacy endpoints were assessed at 1 month post treatment. Results: Nine patients were enrolled in the 3 cohort dose escalation study. There were no dose-limiting toxicities and the drug dose and light fluence for treatment was determined. No photosensitivity reactions were observed at any drug dose during solar simulator testing. Four patients experienced 3 SAEs that were probably or possibly related to treatment including oral pain, tumor hemorrhage, and tumor pain. For 8 patients who were assessed for best overall response rate after a single cycle of treatment using clinical and RECIST 1.1, the objective response rate (ORR) was 75% (6/8) with 3 complete responses which were durable (4-16 months). The disease control rate was 100% (DCR). 7/8 patients showed a decrease in tumor density, consistent with post-treatment necrosis. Conclusions: The phase 1 dose escalation study demonstrated the safety and tolerability of photoimmunotherapy with RM1929. We have observed improvement in clinically significant endpoints in patients with rHNSCC who do not have other treatment options. Clinical trial identification: NCT02422979 Legal entity responsible for the study: FDA Funding: Aspyrian Therapeutics Disclosure: All authors have declared no conflicts of interest.