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
5105 - Fresh blood Immune cell monitoring in patients treated with nivolumab in the GETUG-AFU26 NIVOREN study: association with toxicity and treatment outcome
Presenter: Aude DESNOYER
Session: Poster Display session 3
Resources:
Abstract
1877 - Advanced clear-cell renal cell carcinoma (accRCC): association of microRNAs (miRNAs) with molecular subtypes, mRNA targets and outcome.
Presenter: Annelies Verbiest
Session: Poster Display session 3
Resources:
Abstract
5543 - Prior tyrosine kinase inhibitors (TKI) and antibiotics (ATB) use are associated with distinct gut microbiota ‘guilds’ in renal cell carcinoma (RCC) patients
Presenter: Valerio Iebba
Session: Poster Display session 3
Resources:
Abstract
2689 - mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
Presenter: Cristina Suarez Rodriguez
Session: Poster Display session 3
Resources:
Abstract
3069 - Efficacy of immune checkpoint inhibitors (ICI) and genomic alterations by body mass index (BMI) in Advanced Renal Cell Carcinoma (RCC)
Presenter: Aly-Khan Lalani
Session: Poster Display session 3
Resources:
Abstract
5089 - Finding the Right Biomarker for Renal Cell Carcinoma (RCC): Nivolumab treatment induces the expression of specific peripheral lymphocyte microRNAs in patients with durable and complete response.
Presenter: Lorena Incorvaia
Session: Poster Display session 3
Resources:
Abstract
2594 - Algorithms derived from quantitative pathology can be a gatekeeper in patient selection for clinical trials in localised clear cell renal cell carcinoma (ccRCC)
Presenter: In Hwa Um
Session: Poster Display session 3
Resources:
Abstract
2566 - High baseline blood volume is an independent favorable prognostic factor for overall and progression-free survival in patients with metastatic renal cell carcinoma
Presenter: Aska Drljevic-nielsen
Session: Poster Display session 3
Resources:
Abstract
2675 - Impact of estimand selection on adjuvant treatment outcomes in renal cell carcinoma (RCC)
Presenter: Daniel George
Session: Poster Display session 3
Resources:
Abstract
1541 - TERT gene fusions characterize a subset of metastatic Leydig cell tumors
Presenter: Bozo Kruslin
Session: Poster Display session 3
Resources:
Abstract