3725 - Intratumoral and peripheral exploratory biomarker analysis in patients with locoregional, recurrent head and neck squamous cell carcinoma (rHNSCC) treated with RM-1929 photoimmunotherapy

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.