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
4021 - Prospective pathological experience with research biopsies in the context of clinical trials at Vall d’Hebron Institute of Oncology
Presenter: Paolo Nuciforo
Session: Poster Display session 3
Resources:
Abstract
5603 - Development of a comprehensive next-generation targeted sequencing assay for detection of gene-fusions in solid tumors
Presenter: Vinay Mittal
Session: Poster Display session 3
Resources:
Abstract
4952 - Next-generation sequencing for better treatment strategy of cancer of unknown primary (CUP)
Presenter: Kang Kook Lee
Session: Poster Display session 3
Resources:
Abstract
4590 - Circulating-free DNA analysis from long-term surviving metastatic colorectal cancer patients undergoing surgery for resectable disease.
Presenter: Michele Ghidini
Session: Poster Display session 3
Resources:
Abstract
3696 - Ultra-sensitive detection of circulating tumor DNA identifies patients in high risk of recurrence in early stages melanoma
Presenter: Filip Janku
Session: Poster Display session 3
Resources:
Abstract
4295 - Identification of the founder BRCA1 mutation c.4117G>T (p.Glu1373*) recurring in Abruzzo and Lazio regions of Central Italy and predisposing to breast/ovarian and BRCA1-related cancers
Presenter: Daniela Di Giacomo
Session: Poster Display session 3
Resources:
Abstract
2214 - Enzalutamide (ENZA) and Apalutamide (APA) In vitro chemical reactivity studies and Activity in a Mouse Drug Allergy Model (MDAM)
Presenter: Mausumee Guha
Session: Poster Display session 3
Resources:
Abstract
5044 - Influence of genetic variation in COMT on cisplatin-induced nephrotoxicity in cancer patients.
Presenter: Bram Agema
Session: Poster Display session 3
Resources:
Abstract
3293 - Cardioprotective and anti-inflammatory effects of Empagliflozin during treatment with Doxorubicin: a cellular and preclinical study
Presenter: Vincenzo Quagliariello
Session: Poster Display session 3
Resources:
Abstract
3324 - Breast Cancer Organoids Model Treatment Response of HER2 Targeted Therapy in HER2-mutant Breast Cancer
Presenter: Xuelu Li
Session: Poster Display session 3
Resources:
Abstract