A phase I, single-center, open-label study of RM-1929 photoimmunotherapy in Japanese patients with recurrent head and neck squamous cell carcinoma

Makoto Tahara,Susumu Okano,Wataru Okano,Takao Fujisawa,Toshifumi Tomioka,Ryuichi Hayashi,Takeshi Shinozaki,Yuri Ueda,Merrill A Biel,Kosuke Ishida,Tomohiro Enokida

doi:10.1007/s10147-021-01960-6

Abstract

BackgroundTo determine the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of a single cycle of RM-1929 photoimmunotherapy, an anti-EGFR antibody cetuximab conjugated with a light-activatable dye (IRDye®700DX), in Japanese patients with recurrent head and neck squamous cell carcinoma (rHNSCC).MethodsPatients received a single fixed dose (640 mg/m2) of RM-1929 and a fixed light treatment dose (50 J/cm2 for superficial illumination; 100 J/cm fiber diffuser length for interstitial illumination). Safety, tumor response (modified RECIST v1.1 by central radiology review), pharmacokinetics, and immunogenicity were evaluated.ResultsThree Japanese patients were enrolled who had failed ≥ 3 prior lines of therapy including radiation, chemotherapy, cetuximab, and immunotherapy. Target lesions were: submental lesion; right superficial cervical node lesion and oropharynx lesion; and external auditory canal lesion. All patients experienced ≥ 1 treatment-emergent adverse event (TEAE), but none were considered dose-limiting. TEAEs were mild to moderate in severity except for one grade 3 application-site pain, which was transient, resolved without sequelae within 24 h, and did not affect study treatment administration. Thirteen of 17 TEAEs reported were possibly or probably related to study treatment. Three patient reports of application-site pain and localized edema were deemed probably related to study treatment. Objective response was observed in two patients (both partial responses). The third patient had disease progression. RM-1929 concentrations and pharmacokinetic parameters were similar in all patients. No patients tested positive for anti-drug antibodies.ConclusionsRM-1929 photoimmunotherapy showed a manageable safety profile in rHNSCC. Tumor response in these heavily pre-treated patients was clinically meaningful and warrants further investigation.Clinical trial registrationThe trial was registered with the Japanese registry of clinical trials as jRCT2031200133.

Highlights

Head and neck cancers, including cancers of the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx, are the seventh most common cancer worldwide, accounting for nearly 900,000 new cancer cases each year [1, 2]
All patients had failed to respond to ≥ 3 lines of prior therapy including radiation, chemotherapy, cetuximab and immunotherapy
AUC0 –∞ area under the plasma concentration–time curve, CL clearance, Cmax maximum plasma concentration, n/a not available, CV% % coefficient of variation, T1/2 terminal half-life, Tmax time to achieve Cmax, SD standard deviation, Vss volume of distribution at steady state a Median and range relative to start of infusion b Using predicted AUC0 –∞, CL, and Vss in response to photosensitivity (MED) testing

Summary

Introduction

Head and neck cancers, including cancers of the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx, are the seventh most common cancer worldwide, accounting for nearly 900,000 new cancer cases each year [1, 2]. 70% of patients with primary HNSCC present with locally or regionally advanced disease (stage III or IV) [6], which recurs in approximately 40–65% of cases after primary therapy with surgery and radiation, with or without chemotherapy [6,7,8,9,10]. Preliminary efficacy, pharmacokinetics, and immunogenicity of a single cycle of RM-1929 photoimmunotherapy, an anti-EGFR antibody cetuximab conjugated with a light-activatable dye (IRDye®700DX), in Japanese patients with recurrent head and neck squamous cell carcinoma (rHNSCC). Three patient reports of application-site pain and localized edema were deemed probably related to study treatment. Conclusions RM-1929 photoimmunotherapy showed a manageable safety profile in rHNSCC Tumor response in these heavily pre-treated patients was clinically meaningful and warrants further investigation. Clinical trial registration The trial was registered with the Japanese registry of clinical trials as jRCT2031200133

Methods

Results

Discussion

Conclusion