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, 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

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.

Conflict of interest statement

David M. Cognetti: Honoraria (Intuitive Surgical); Consulting or Advisory Role (Rakuten Medical). Jennifer M. Johnson: Consulting or Advisory Role (Bristol‐Myers Squibb; Foundation Medicine; Rakuten Medical); Research Funding (AstraZeneca; Bristol‐Myers Squibb; Merck). Joseph M. Curry: Consulting or Advisory Role (Rakuten Medical); Research Funding (AstraZeneca; Castle Biosciences). Samith T. Kochuparambil: none. Darren McDonald: Consulting or Advisory Role (Rakuten Medical). Frank Mott: none. Mary J. Fidler: Honoraria (AstraZeneca); Consulting or Advisory Role (AstraZeneca; Genentech; G1 Therapeutics, Rakuten Medical); Speakers' Bureau (Merck; Genentech); Research Funding (Biodesix; Pfizer). Kerstin Stenson: Stock or Other Ownership (Abbott; Abbvie; Biogen; Bristol‐Myers Squibb; Celgene); Honoraria (UpToDate); Travel, Accommodations, Expenses (Rakuten Medical). Nilesh R. Vasan: Employment (Adroit Surgical LLC); Leadership (Adroit Surgical LLC); Stock or Other Ownership (Adroit Surgical LLC); Patents, Royalties, Other Intellectual Property (Adroit Surgical LLC; University of Oklahoma Board of Regents). Mohammad A. Razaq: Honoraria (AstraZeneca); Speakers' Bureau (Merck & Co); Stock or Other Ownership (Amgen); Travel, Accommodation, Expenses (Merck). John Campana: Travel, Accommodations, Expenses (Axogen). Patrick Ha: Consulting or Advisory Role (Bayer/LOXO Oncology, Rakuten Medical); Travel, Accommodations, Expenses (Genentech). Educational funding (Stryker, Johnson & Johnson, Medtronic, Axogen). Grace Mann: Employment (Rakuten Medical); Stock or Other Ownership (Rakuten Medical). Kosuke Ishida: Employment (Rakuten Medical; Boehringer Ingelheim). Miguel Garcia‐Guzman: Employment (Rakuten Medical); Leadership (Rakuten Medical); Stock or Other Ownership (Vertex Pharma; Gilead); Patents, Royalties, Other Intellectual Property (UC Irvine; Rakuten Medical). Merrill Biel: Employment (Rakuten Medical); Leadership (Rakuten Medical); Stock and Other Ownership Interests (Rakuten Medical); Travel, Accommodation, Expenses (Rakuten Medical). Ann M. Gillenwater: Consulting or Advisory Role (Rakuten Medical Inc., Masimo Corporation).

© 2021 The Authors. Head & Neck published by Wiley Periodicals LLC.

Figures

FIGURE 1
FIGURE 1
Mechanism of action and RM‐1929 photoimmunotherapy overview. (A) A tumor‐targeted antibody is conjugated with a light‐activatable dye. Following infusion into the body, the tumor is illuminated with non‐thermal red light (690 nm), leading to anticancer activity mediated by biophysical processes that damage the membrane integrity of cells. (B) Tumor illumination is performed 24 ± 4 h after antibody conjugate infusion. Cylindrical diffusers placed in needle catheters are used to treat interstitial tumors (B1, B2), while frontal diffusers are used to treat superficial tumors (B3, B4). Light illumination of the tumor is administered 24 ± 4 h after RM‐1929 infusion to allow for drug distribution within the tumor. The non‐thermal red light is applied to the tumor using a (1) frontal diffuser for superficial light illumination for tumors ≤1 cm from the skin or mucosal surface or a (2) cylindrical diffuser for interstitial illumination for tumors >1 cm from the skin or mucosal surface. The illumination time for frontal and cylindrical diffusers is 5 min for each treated area. For interstitial illumination, cylindrical diffusers are placed uniformly into the tumor 1.8 ± 0.2 cm apart using 17‐gauge closed‐tipped needle catheters under radiographic or ultrasound imaging
FIGURE 2
FIGURE 2
Efficacy outcomes following RM‐1929 photoimmunotherapy in study Part 2 patients (n = 30) with locoregional rHNSCC. (A) Waterfall plot of best change in sum of diameters of target lesions from baseline by central radiology assessment; (B) Kaplan–Meier plot of overall survival; and (C) Swimmer plot of individual patient survival. Arrowed bars represent patients who were censored at last contact date. *One enrolled patient did not have post‐baseline scans. **Lesions completely resolved, and lymph nodes were <10 mm. Target lesions were defined as lesions identified by the investigator that were light illuminated. Non‐target lesions, including lung metastases, did not undergo light illumination and further discussion on change in tumor size of non‐target lesions can be found in Appendix S1. Tumor locations were determined by a sponsor clinical expert based on target and non‐target lesions reported in the study
FIGURE 3
FIGURE 3
Clinical course of patients with locoregional rHNSCC treated with RM‐1929 photoimmunotherapy: Patient 1 with recurrent left facial cancer; Patient 2 with bilateral intraoral recurrent tumors and neck dermal metastases; and Patient 3 with a tongue tumor

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