Abstract 2954
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 T1/2 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.
Resources from the same session
2927 - Singapore Caregiver Quality Of Life Scale (SCQOLS): Turkish Validity and Reliability Study
Presenter: Nur Basak
Session: Poster Display session 3
Resources:
Abstract
5066 - Screening for Psicosocial Distress in recently diagnosed cancer patients
Presenter: Eva Baillès
Session: Poster Display session 3
Resources:
Abstract
6074 - Socio-demographic characteristics and quality of life analysis of cancer survivors followed at a Primary Care Center.
Presenter: Begona Grana Suarez
Session: Poster Display session 3
Resources:
Abstract
5129 - The adhesion in the screening measures in carrying patients of breast cancer and ovary hereditary and the relationship with the psychological aspects
Presenter: Melinda Concepcion
Session: Poster Display session 3
Resources:
Abstract
5635 - Assessment of emotional discomfort of oncological patients in the first nursing visit at Donostia University Hospital
Presenter: Elena Uranga
Session: Poster Display session 3
Resources:
Abstract
858 - A systematic review and meta-analysis of the distress thermometer for the screening of distress in Chinese patients with cancer
Presenter: Hui Hui Sun
Session: Poster Display session 3
Resources:
Abstract
4475 - Pharmacist and Nurse (PN) Led Melanoma Immunotherapy Clinic: Patient Experience Survey
Presenter: Dharmisha Chauhan
Session: Poster Display session 3
Resources:
Abstract
1871 - Phone Triage & Acute Review Clinics: The emerging role of the Oncology Specialist Nurse
Presenter: Fiona Barrett
Session: Poster Display session 3
Resources:
Abstract
5193 - Patient reported outcomes during immunotherapy: symptom burden in daily clinical practice
Presenter: José Koldenhof
Session: Poster Display session 3
Resources:
Abstract
2453 - Factors related to hospital length of stay, re-admissions and unplanned care for patients with cancer, an on-going study
Presenter: Helena Ullgren
Session: Poster Display session 3
Resources:
Abstract