Abstract 5299
Background
Tumor microenvironment represents 20-60% of solid tumor mass and is increasingly recognized to play a key role in promotion, invasiveness and metastasis. Mounting evidence suggests that FAP-expressing CAFs, the predominant stroma cell type, is involved in the tumor immune response. A novel antibody-drug conjugate, OMTX705, was generated through CYS-based conjugation of a new anti-FAP humanized antibody, with high specificity and affinity, to a novel cytolysin, using an optimized vcPABA linker.
Methods
In vivo studies were performed in patient-derived xenograft models for pancreatic and NSCL cancer in immunodeficient and humanized mice. Tumor volume and animal weight were monitorized 3 times a week over 4 weeks of treatment with OMTX705, administered intravenously at different doses, either as single agent or in combination with chemotherapy such as Gemcitabine or Paclitaxel, or immunotherapy such as Pembrolizumab. FACS and IHC analysis of CD45, CD25, CD3, CD4, CD8 and Fox3P markers were performed on blood and tumor samples to study the effect of OMTX705 on immune system in these models.
Results
OMTX705 showed 100% tumor growth inhibition and regression in the PDX murine models for pancreatic and NSCL cancer, both as single agent and in combination with Gemcitabine and Nab-Paclitaxel, Paclitaxel, or Pembrolizumab, without weight loss. When treated with OMTX705 in combination with chemotherapy, the response was maintained for a longer period without further treatment: re-growth of tumors was delayed and tumors kept responding upon re-treatment, showing lack of resistance to OMTX705 treatment. In combination with Pembrolizumab immunotherapy in a humanized PDX model for lung cancer, OMTX705 efficacy was even higher at lower dose, inducing full regression and significant delay in tumor recurrence, through CD8(+) T cell dependent immunomodulation.
Conclusions
FAP-targeted OMTX705 represents a potent novel strategy for cancer treatment at invasive stages. Due to the broad expression of FAP in the tumor microenvironment of a wide array of carcinomas, OMTX705 is a highly promising candidate to treat different solid tumors with low response to anti-PD1 immunotherapies.
Clinical trial identification
Legal entity responsible for the study
Oncomatryx Biopharma, S.L.
Funding
Oncomatryx Biopharma, S.L.
Editorial Acknowledgement
Disclosure
M. Fabre, C. Ferrer, S. Dominguez-Hormaetxe, L. Simon: Employment: Oncomatryx Biopharma, S.L. R. Kontermann, K. Pfizenmaier, M. Hidalgo: Member scientific advisory board: Oncomatryx Biopharma, S.L. M. Abbas: Employee: Tube Pharmaceuticals, GmBH. W. Richter: Employee and shareholder: Tube Pharmaceuticals, GmBH. All other authors have declared no conflicts of interest.
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