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
5031 - Sarcoidosis-Like Reaction Mimics Progression in patients treated with immune checkpoint inhibitors
Presenter: Sophie Hans
Session: Poster Display session 3
Resources:
Abstract
5650 - Tissue-based activation of mucosal-associated invariant T (MAIT) cells in combination ipilimumab and nivolumab checkpoint inhibitor (CI) colitis.
Presenter: Sarah Sasson
Session: Poster Display session 3
Resources:
Abstract
5944 - Significance of severe immune-related adverse effects (irAE) on patients with advanced tumors treated with immune checkpoint inhibitors being admitted for secondary toxicity: Clinical relevance and next steps
Presenter: Leyre Zubiri
Session: Poster Display session 3
Resources:
Abstract
5989 - Implementation of a dedicated immuno-oncology toxicity service reduces the acute impact of immune-related adverse events
Presenter: Anna Olsson-Brown
Session: Poster Display session 3
Resources:
Abstract
3267 - Cardiotoxic and pro-inflammatory effects induced by the association of immune checkpoint inhibitor Pembrolizumab and Trastuzumab in preclinical models
Presenter: Nicola Maurea
Session: Poster Display session 3
Resources:
Abstract
3417 - Interstitial lung disease associated with immune-checkpoint inhibitors in malignant diseases
Presenter: Akira Yamagata
Session: Poster Display session 3
Resources:
Abstract
2071 - A Phase 1 Study of Intraperitoneal MCY-M11 Anti-Mesothelin CAR for Women with Platinum Resistant High Grade Serous Adenocarcinoma of the Ovary, Primary Peritoneum, or Fallopian Tube, or Subjects with Peritoneal Mesothelioma with Recurrence after Prior Chemotherapy
Presenter: Christina Annunziata
Session: Poster Display session 3
Resources:
Abstract
4935 - Trial in progress: First-in-human study of a novel anti-NY-ESO-1–anti-CD3, TCR-based bispecific (IMCnyeso) as monotherapy in NY-ESO-1/LAGE-1A-positive advanced solid tumors (IMCnyeso-101)
Presenter: Juanita Lopez
Session: Poster Display session 3
Resources:
Abstract
5613 - Nimotuzumab-Cisplatin-Radiation versus Cisplatin-Radiation in HPV negative oropharyngeal cancer
Presenter: Kumar Prabhash
Session: Poster Display session 3
Resources:
Abstract
2576 - Interim analysis of a single arm phase 2 study of adjuvant nivolumab after salvage resection in head and neck squamous cell carcinoma patients previously treated with definitive therapy.
Presenter: Trisha Wise-draper
Session: Poster Display session 3
Resources:
Abstract