2954 - Integrated data review evaluating safety, pharmacokinetics (PK) and immunogenicity of RM-1929 photoimmunotherapy (PIT) in subjects with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC).

Background

RM-1929 photoimmunotherapy (PIT) consists of the EGFR-directed antibody cetuximab conjugated to a dye (IRDye^® 700DX). Binding of the antibody-dye conjugate to cancer cells followed by photoactivation with non-thermal red light induces selective and rapid tumour cell death.

Methods

An integrated analysis of safety, PK, and immunogenicity was conducted in subjects with rHNSCC who received RM-1929 PIT in Phase 1 and Phase 1/2a trials.

Results

Forty-one subjects were treated with RM-1929 PIT. There were no dose-limiting toxicities or clinically significant shifts in chemistry, hematology, or ECGs. The observed TEAEs by grade were: Grade 1 – 97.6% (40/41); Grade 2 – 85.4% (35/41); Grade 3 – 58.5% (24/41); Grade 4 – 12.2% (5/41); and Grade 5 – 7.3% (3/41). The most frequent TEAEs (>15% incidence) included fatigue, application site pain, dysphagia, constipation, cough, erythema, and face edema. Three photosensitivity reactions were observed. All Grade 4 TEAEs (anemia, myocardial infarction, sepsis, hypoglycemia, tumor hemorrhage, obstructive airway and pneumothorax) resolved. 41.5% (17/41) of subjects experienced SAEs, while 12.2% (5/41) were considered treatment related SAEs (oral pain, tumor pain, obstructive airways disorder, and tumor hemorrhage-non fatal). Three subjects experienced SAEs that led to death (pneumonia, tumor hemorrhage, and arterial hemorrhage) that were considered unrelated to treatment due to the late onset of the events. PK analysis showed that RM-1929 exposure (AUC) increased with escalating doses in a dose proportional manner. At 640 mg/m² RM-1929 dose, AUC reaches a range expected to achieve full saturation of EGFR binding in tissues when compared to a single 250 mg/m² dose of Erbitux. In subsequent cycles, the mean CL, Vss and T_1/2 estimates appeared comparable to those in Cycle 1. Immunogenicity (anti-drug antibody) was detected in 9.5% (4/42) of subjects, 3 of which emerged post-treatment.

Conclusions

The integrated clinical safety data indicated that RM-1929 PIT treatment had a favorable safety profile with no unexpected safety concerns.

Clinical trial identification

NCT02422979.

Editorial acknowledgement

Legal entity responsible for the study

Rakuten Medical, Inc.

Funding

Rakuten Medical, Inc.

Disclosure

J.M. Johnson: Advisory / Consultancy: Foundation Medicine; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca. J.M. Curry: Research grant / Funding (institution): AstraZeneca. S.T. Kochuparambil: Shareholder / Stockholder / Stock options, Full / Part-time employment: Minnesota Hematology Oncology; Advisory / Consultancy: BMS. D.R. McDonald: Travel / Accommodation / Expenses, Formerly Rakuten Aspyrian: Rakuten Medical, Inc. M.J. Fidler: Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Guardant Health; Honoraria (self), Advisory / Consultancy: AstraZeneca; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (self): Biodesix. N.R. Vasan: Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties: Adroit Surgical, LLC. M.A. Razaq: Shareholder / Stockholder / Stock options: AbbVie; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses, previously Rakuten Aspyrian: Rakuten Medical. M. Tahara: Honoraria (self): Merck Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): BMS; Honoraria (self): Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Ono Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (self): MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy, (previously Rakuten Aspyrian): Rakuten Medical; Research grant / Funding (self): Loxo; Research grant / Funding (self): Novartis. M.A. Biel: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Rakuten Medical, Inc. M. Tello: Shareholder / Stockholder / Stock options, Full / Part-time employment: Rakuten Medical, Inc. M. Garcia-Guzman: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Rakuten Medical, Inc. E. Sun: Shareholder / Stockholder / Stock options, Full / Part-time employment: Rakuten Medical, Inc. A.M. Gillenwater: Advisory / Consultancy: Sanofi; Advisory / Consultancy: Masimo; Advisory / Consultancy: Novartis; Travel / Accommodation / Expenses, Previously Rakuten Aspyrian: Rakuten Medical, Inc.; Travel / Accommodation / Expenses: IAOO Conference. All other authors have declared no conflicts of interest.