Abstract 2661
Background
Tumor stroma represents 20-60% of solid tumor mass and plays a key role in promotion, invasiveness and metastasis. FAP-expressing CAFs, the predominant stroma cell type, are involved in tumor immune response. A novel antibody-drug conjugate, OMTX705, was generated through CYS-based conjugation of a new anti-FAP humanized antibody to a novel cytolysin using an optimized vcPABA linker.
Methods
In vivo studies were performed in patient-derived xenograft models for NSCL cancer in humanized mice. Tumor volume and animal weight were monitored over 4-week treatment with OMTX705 administered intravenously at different doses, alone or combined with Pembrolizumab. FACS and IHC analysis of markers for immune cells, CAFs, and cell proliferation or apoptosis, were performed on tumor samples to study OMTX705 effect on tumor stroma and elucidate its mechanism of action. In vitro assays were performed to support in vivo data. OMTX705 stability in blood was determined after i.v administration in CD1 mice.
Results
OMTX705 showed 100% tumor growth inhibition and higher activity than Pembrolizumab in the humanized PDX model for NSCL cancer without weight loss. Full tumor regression was found in 10% of mice treated with OMTX705 alone and 20% in combination with Pembrolizumab. A significant delay in tumor recurrence was observed. OMTX705 was 100% stable in bloodstream after 7 days. FACS analysis evidenced a significant increase in CD8(+) T cell tumor infiltration. Results from in vitro studies and IHC analysis of tumors identified CAFs as highly specific reservoir cells for OMTX705 from which the high potent cytolysin payload is released to induce apoptosis of adjacent tumor cells and CD8(+) T cell immunomodulation.
Conclusions
OMTX705 alone induces tumor shrinkage, and full regression with Pembrolizumab, through highly specific, CAF-dependent and long-lasting modulation of tumor stroma. This novel mechanism of action makes OMTX705 a potent and innovative strategy for NSCL cancer treatment. Considering FAP is expressed in a wide array of carcinomas, OMTX705 represents a highly promising and well-tolerated candidate to treat solid tumors with low response to anti-PD1 immunotherapies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Oncomatryx Biopharma, S.L.
Funding
Oncomatryx Biopharma, S.L.
Disclosure
M. Fabre: Full / Part-time employment: Oncomatryx Biopharma, S.L. C. Ferrer: Full / Part-time employment: Oncomatryx Biopharma, S.L. S. Domínguez-Hormaetxe: Full / Part-time employment: Oncomatryx Biopharma, S.L. R. Kontermann: Advisory / Consultancy: Oncomatryx Biopharma, S.L.; Advisory / Consultancy: SunRock Biopharma, S.L.; Advisory / Consultancy: Roche. K. Pfizenmaier: Advisory / Consultancy: Oncomatryx Biopharma, S.L.; Advisory / Consultancy: SunRock Biopharma, S.L. O. Seifer: Research grant / Funding (institution): Oncomatryx Biopharma, S.L. M.D. Vivanco: Research grant / Funding (institution): Oncomatryx Biopharma, S.L. S. Lee: Research grant / Funding (institution): Oncomatryx Biopharma, S.L. P. López-Casas: Full / Part-time employment: Bioncotech Therapeutics, S.L. M. Abbas: Full / Part-time employment: Tube Pharmaceuticals GmBH. W. Richter: Advisory / Consultancy: Oncomatryx Biopharma, S.L.; Shareholder / Stockholder / Stock options, Full / Part-time employment: Tube Pharmaceuticals GmBH. L. Simon: Honoraria (self), Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment, Patents: Oncomatryx Biopharma, S.L.; Honoraria (self), Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment, Patents: Patia Biopharma, SA de CV; Honoraria (self), Leadership role, Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Patia Europe, S.L.; Shareholder / Stockholder / Stock options, Full / Part-time employment: PatiaCan, SA de CV; Honoraria (self), Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Permedika Entrepeneurs; Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options: SunRock Biopharma, S.L.; Licensing / Royalties, Patents: Quimatryx, S.L.; Shareholder / Stockholder / Stock options: Stemcell Therapeutics, S.L.; Shareholder / Stockholder / Stock options: Helenes Ventures, S.L.; Shareholder / Stockholder / Stock options: Nellum Corp. M. Hidalgo: Advisory / Consultancy: Oncomatryx Biopharma, S.L.; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: Champions Oncology; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: Pharmacite Biotech; Shareholder / Stockholder / Stock options: BioOncotech; Shareholder / Stockholder / Stock options: Nelum; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self): MSD Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BiolineRX; Honoraria (self), Advisory / Consultancy: Roche/Genentech; Honoraria (self), Advisory / Consultancy: SOBI; Honoraria (self), Advisory / Consultancy: Agenus; Honoraria (self), Advisory / Consultancy: Erytech Pharma; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca/MedImmune; Advisory / Consultancy, Travel / Accommodation / Expenses: Menarini; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Research grant / Funding (self): Bicycle Therapeutics; Research grant / Funding (self): Asana Biosciences.
Resources from the same session
4489 - A Window of Opportunity Trial of Atorvastatin Targeting p53 Mutant Malignancies
Presenter: Joaquina Baranda
Session: Poster Display session 3
Resources:
Abstract
1945 - Randomized Phase II Study of Trabectedin/Olaparib Compared to Physician’s Choice in Subjects with Previously Treated Advanced or Recurrent Solid Tumors Harboring DNA Repair Deficiencies.
Presenter: Christoph Heilig
Session: Poster Display session 3
Resources:
Abstract
3021 - Homogenisation of Leftover Surgical Tissue across multiple cancer types: a Feasibility Study (HoLST-F)
Presenter: Lavinia Spain
Session: Poster Display session 3
Resources:
Abstract
2882 - Safety, efficacy, and immune effects of intratumoral tilsotolimod in patients with refractory solid tumors: updated results from ILLUMINATE-101
Presenter: Hani Babiker
Session: Poster Display session 3
Resources:
Abstract
1950 - Phase 1 Dose Escalation of MSC-1, a humanized anti-LIF monoclonal antibody, in patients (pts) with advanced solid tumors: Updated results
Presenter: Erkut Borazanci
Session: Poster Display session 3
Resources:
Abstract
2391 - A phase 1 study of Sym021, an anti-PD-1 antibody (Ab), alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3)
Presenter: Anna Spreafico
Session: Poster Display session 3
Resources:
Abstract
5692 - FPA150 (B7-H4 antibody) Phase 1 Update in Advanced Solid Tumors: Monotherapy and in Combination with Pembrolizumab
Presenter: Zev Wainberg
Session: Poster Display session 3
Resources:
Abstract
2416 - MG1124, a novel CEACAM1-targeted monoclonal antibody, has therapeutic potential as a combination partner of PD-1 inhibitors in NSCLC patients
Presenter: Eun Hee Lee
Session: Poster Display session 3
Resources:
Abstract
3681 - Durvalumab + monalizumab, mFOLFOX6, and bevacizumab in patients (pts) with metastatic microsatellite-stable colorectal cancer (MSS-CRC)
Presenter: May Cho
Session: Poster Display session 3
Resources:
Abstract
2664 - Phase (Ph) II study of MBG453 + spartalizumab in patients (pts) with non-small cell lung cancer (NSCLC) and melanoma pretreated with anti–PD-1/L1 therapy
Presenter: Nicholas Mach
Session: Poster Display session 3
Resources:
Abstract