Phase 1/2a, open-label, multicenter study of RM-1929 photoimmunotherapy in patients with locoregional, recurrent head and neck squamous cell carcinoma

David M Cognetti; Jennifer M Johnson; Joseph M Curry; Samith T Kochuparambil; Darren McDonald; Frank Mott; Mary J Fidler; Kerstin Stenson; Nilesh R Vasan; Mohammad A Razaq; John Campana; Patrick Ha; Grace Mann; Kosuke Ishida; Miguel Garcia-Guzman; Merrill Biel; Ann M Gillenwater

doi:10.1002/hed.26885

Phase 1/2a, open-label, multicenter study of RM-1929 photoimmunotherapy in patients with locoregional, recurrent head and neck squamous cell carcinoma

Head Neck. 2021 Dec;43(12):3875-3887. doi: 10.1002/hed.26885. Epub 2021 Oct 9.

Authors

David M Cognetti^{1

2}, Jennifer M Johnson^{2

3}, Joseph M Curry^{1

2}, Samith T Kochuparambil⁴, Darren McDonald⁵, Frank Mott⁶, Mary J Fidler⁷, Kerstin Stenson⁸, Nilesh R Vasan⁹, Mohammad A Razaq¹⁰, John Campana¹¹, Patrick Ha¹², Grace Mann¹³, Kosuke Ishida¹⁴, Miguel Garcia-Guzman¹⁵, Merrill Biel¹³, Ann M Gillenwater¹⁶

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
² Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
³ Department of Medical Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
⁴ Department of Medical Oncology, Virginia Piper Cancer Institute, Minneapolis, Minnesota, USA.
⁵ Department of Otolaryngology-Head and Neck Surgery, Virginia Piper Cancer Institute, Minneapolis, Minnesota, USA.
⁶ Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
⁷ Department of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, Illinois, USA.
⁸ Department of Otorhinolaryngology, Rush University Medical Center, Chicago, Illinois, USA.
⁹ Department of Otolaryngology-Head and Neck Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
¹⁰ Division of Hematology and Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
¹¹ Department of Otolaryngology, University of Colorado Head and Neck Specialists, Denver, Colorado, USA.
¹² Division of Head and Neck Surgical Oncology, University of California San Francisco, San Francisco, California, USA.
¹³ Department of Clinical Development, Rakuten Medical, Inc, San Mateo, California, USA.
¹⁴ Department of Biostatistics, Rakuten Medical Japan, Tokyo, Japan.
¹⁵ Department of Translational Sciences, Rakuten Medical, Inc, San Diego, California, USA.
¹⁶ Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Abstract

Background: Recurrent head and neck squamous cell carcinoma (rHNSCC) represents a significant global health burden with an unmet medical need. In this study we determined the safety and efficacy of RM-1929 photoimmunotherapy in patients with heavily pretreated rHNSCC.

Methods: RM-1929 (anti-EGFR-IR700 dye conjugate) was infused, followed by tumor illumination. We evaluated safety, tumor response, and pharmacokinetics.

Results: Nine patients were enrolled in Part 1 (dose-finding) and 30 patients in Part 2 (safety and efficacy). No dose-limiting toxicities were experienced in Part 1; 640 mg/m² with fixed light dose (50 J/cm² or 100 J/cm) was recommended for Part 2. Adverse events (AEs) in Part 2 were mostly mild to moderate but 19 (63.3%) patients had AE ≥Grade 3, including 3 (10.0%) with serious AEs leading to death (not treatment related). Efficacy in Part 2: unconfirmed objective response rate (ORR) 43.3% (95% CI 25.46%-62.57%); confirmed ORR 26.7% (95% CI 12.28%-45.89%); median overall survival 9.30 months (95% CI 5.16-16.92 months).

Conclusions: Treatment was well tolerated. Responses and survival following RM-1929 photoimmunotherapy in heavily pretreated patients with rHNSCC were clinically meaningful and warrant further investigation.

Clinical trial information: NCT02422979.

Keywords: RM-1929 photoimmunotherapy; cetuximab-IR700 conjugate; light-activatable dye (IRDye 700DX); recurrent head and neck squamous cell carcinoma (rHNSCC); tumor-targeted monoclonal antibody.

Publication types

Clinical Trial, Phase I
Clinical Trial, Phase II
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Combined Chemotherapy Protocols
Cetuximab / therapeutic use
Head and Neck Neoplasms* / therapy
Humans
Immunotherapy*
Neoplasm Recurrence, Local* / drug therapy
Phototherapy
Squamous Cell Carcinoma of Head and Neck* / therapy

Substances

Cetuximab

Associated data

ClinicalTrials.gov/NCT02422979