A Phase 2a, Multicenter, Open-Label Study of RM-1929 Photoimmunotherapy in Patients With Recurrent Head And Neck Cancer

Abstract

Patients with recurrent head and neck squamous cell cancer (rHNSCC) have poor prognoses and limited treatment options after they have failed standard therapies. We are investigating photoimmunotherapy (PIT) for the treatment of rHNSCC using a novel targeted light-activated drug conjugate RM1929, consisting of the EGFR-directed monoclonal antibody cetuximab conjugated to the phthalocyanine dye, IRDye 700DX. This is a multi-institutional open-label Phase 2a study of rHNSCC patients who cannot be satisfactorily treated with surgery, radiation, or platinum chemotherapy. PIT, using a previously determined optimal drug dose and light treatment dose, was performed to evaluate the safety and efficacy associated with repeat dosing of up to 4 treatment cycles, 4-8 weeks apart, in patients with persistence of disease. For each treatment, nonthermal red light was applied to the tumors 24 hours after intravenous infusion of the photoactivated conjugate. The light was applied on the surface for superficial mucosal/cutaneous disease or within the tumor (via fiber optic diffusers placed by ultrasound guidance) for submucosal/subcutaneous or nodal disease. Responses and Progression-Free Survival (PFS) were calculated using CT RECIST 1.1. All CT RECIST 1.1 measurements were determined by an independent blinded radiologist. Nineteen patients with rHNSCC who were treated with RM-1929 PIT and have been followed for at least 3 months were included in the outcome analysis. There were no dose-limiting toxicities or skin photosensitivity reactions observed. No toxicity was noted for normal tissues exposed to therapeutic light treatment. Two reported SAEs, tumor hemorrhage and tumor pain, were assessed as possibly or probably related to treatment. CT RECIST 1.1 demonstrated a PFS of 153 days (5.1 months). Objective response rate (ORR), complete response (CR) and disease control rate (DCR) by CT RECIST 1.1 were 42% (8/19), 26% (5/19) and 84% (16/19) respectively. Photoimmunotherapy with RM1929 in patients with rHNSCC is safe and well-tolerated. CT RECIST 1.1 PFS, ORR, and CR response rates are improved over those of standard of care therapies and encouraging in these patients who have failed standard therapies and have typically recalcitrant disease. Further investigation of this novel therapeutic strategy is warranted and a Phase 3 clinical trial is planned.