Abstract 3725
Background
Photoimmunotherapy (PIT) is a platform technology that utilizes a photoactivatable dye conjugated to a cancer-targeting antibody. RM-1929 is composed of anti-EGFR antibody cetuximab and IRDye® 700DX. Binding of RM-1929 to EGFR followed by tumor illumination with non-thermal red light elicits rapid necrosis of EGFR-expressing cancer cells. RM-1929 PIT treatment was evaluated in a Phase 1/2a trial in patients with rHNSCC who failed multiple standard of care therapies, and demonstrated a favorable safety profile and resulted in positive response rates (Cognetti et al. ASCO 2019). Here we report preliminary data from exploratory biomarker studies from this study.
Methods
Phase 1 included 9 patients and Phase 2a cohort 30 patients. Pre-treatment biopsies and blood were collected within 12 months and 2 weeks prior to treatment, respectively. Post-treatment biopsies and blood samples were collected after cycle 1 and multiple time points during treatment cycles, respectively. EGFR and PD-L1 IHC expression and plasma cytokines levels were measured. PBMCs were phenotyped using innate and adaptive immune-marker panels.
Results
In 25 patients with pre-treatment biopsies, no trend was observed between EGFR expression and best target tumour response. In 12 patients for which pre- and post-treatment biopsies were available, EGFR expression was maintained in residual tumour after RM-1929 PIT treatment. Additionally, treatment was associated with induction of PD-L1 expression in tumour and immune cells in 10 out of 12 cases. In 13 samples tested, elevated baseline plasma cytokine levels were observed in 4 of 7 responders (3 of 4 CR and 1 of 3 PR) and 1 of 6 non-responders (1 of 5 SD and 0 of 1 PD). Immunophenotyping of whole blood showed systemic induction of innate and adaptive immunity (e.g. NK cells, cytokines, lymphocytes, monocytes, CD4 and CD8 T-cells) after treatment in 15 of 18 patients.
Conclusions
Biomarker analysis in this limited data set provided evidence of potential activation of innate and adaptive immunity following RM-1929 PIT treatment. Further evaluation of these biomarkers will be conducted in a Phase 3 trial (NCT03769506).
Clinical trial identification
NCT02422979.
Editorial acknowledgement
Legal entity responsible for the study
Rakuten Medical, Inc.
Funding
Rakuten Medical, Inc.
Disclosure
J.D. Bui: Advisory / Consultancy: Rakuten Medical, Inc.; Advisory / Consultancy, Research grant / Funding (self): Ignyta, Inc.; Shareholder / Stockholder / Stock options: Paramita Therapeutics. N. Suslov: Shareholder / Stockholder / Stock options, Full / Part-time employment: Rakuten Medical, Inc. D. Yadav: Shareholder / Stockholder / Stock options, Full / Part-time employment: Rakuten Medical, Inc. J. Fong: Shareholder / Stockholder / Stock options, Full / Part-time employment: Rakuten Medical, Inc. E. Sun: Shareholder / Stockholder / Stock options, Full / Part-time employment: Rakuten Medical, Inc. M. Haedo: 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.
Resources from the same session
2344 - Lung Cancer in Europe: strengthening policy responses to address unmet needs
Presenter: Mary Bussell
Session: Poster Display session 3
Resources:
Abstract
1359 - Curative treatment timelines for breast, colorectal, lung and prostate cancer: Implications for medical leave coverage
Presenter: Selina Wong
Session: Poster Display session 3
Resources:
Abstract
4433 - Acute Diagnostic Oncology Clinic: A Unique Primary Care-Oncology Service
Presenter: Abhijit Gill
Session: Poster Display session 3
Resources:
Abstract
3506 - THE NEW MUTATIONAL MODEL IN ONCOLOGY. What changes in welfare, clinical practice, research, and regulatory procedures
Presenter: Nicola Normanno
Session: Poster Display session 3
Resources:
Abstract
3350 - Selection of a set of quality indicators (QI) for oncological clinical pathway
Presenter: Aude Fourcade
Session: Poster Display session 3
Resources:
Abstract
4400 - Sustainable drug prices at market launch: policy proposals and their empirical evidence
Presenter: Nora Fanzen
Session: Poster Display session 3
Resources:
Abstract
4118 - Impact of financial considerations on French physicians’ prescription choices for advanced non-small cell lung cancer (NSCLC)
Presenter: Nathalie Olympios
Session: Poster Display session 3
Resources:
Abstract
1340 - The direct medical cost of breast cancer in a Belgian hospital
Presenter: Hannan Lemhouer
Session: Poster Display session 3
Resources:
Abstract
1863 - Does the healthcare system approaches cancer patients for using private services during diagnostic process?
Presenter: Karolina Osowiecka
Session: Poster Display session 3
Resources:
Abstract
2637 - Measuring financial toxicity of cancer in the Italian health care system: initial results of the patient reported outcome for Fighting Financial Toxicity of cancer project (proFFiT).
Presenter: Silvia Riva
Session: Poster Display session 3
Resources:
Abstract