Clovis Oncology Submits Investigational New Drug Applications for Novel Peptide-Targeted Radionuclide FAP-2286 for Therapeutic and Imaging Clinical Trial

  • Initiation of Phase 1/2 clinical study of novel peptide-targeted radionuclide therapy and imaging agent targeting fibroblast activation protein (FAP) expected 1H 2021
  • Will be the first peptide-targeted radionuclide therapy targeting FAP to enter clinical development

BOULDER, CO, USA I December 29, 2020 I Clovis Oncology, Inc. (NASDAQ: CLVS) today announced that the company has completed submission of two Investigational New Drug (IND) applications to the U.S. Food and Drug Administration (FDA) for FAP-2286, the lead compound in its peptide-targeted radionuclide therapy (PTRT) development program. Following clearance of the INDs by FDA, Clovis plans to initiate a Phase 1/2 clinical study of lutetium-177 labeled FAP-2286 (177Lu-FAP-2286) to determine the dose and tolerability of the FAP-targeting therapeutic agent (Phase 1), with expansion cohorts planned in multiple tumor types (Phase 2). FAP-2286 labelled with gallium-68 (68Ga-FAP-2286) will be utilized as a diagnostic to identify patients with fibroblast activation protein (FAP)-positive tumors appropriate for treatment with the therapeutic agent.

“Submission of these INDs is a very important milestone in the development of FAP-2286, the first clinical candidate from our PTRT platform,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “Targeted radiopharmaceuticals represent an emerging therapeutic class and an area of significant interest to the clinical community, and FAP is considered a target of particular interest given its high, selective expression in multiple solid tumors. We are enthusiastic about the opportunity to become a leader in the rapidly evolving field of PTRT, and the first to begin clinical development of a peptide-targeted radionuclide therapy targeting FAP.”

Fibroblast activation protein (FAP) is a cell-surface protein that is expressed in limited amounts by normal tissues, but highly expressed in cancer-associated fibroblasts (CAFs) present in the tumor microenvironment of many epithelial cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas.i,ii,iii Preclinical data demonstrate that 177Lu-FAP-2286 potently and selectively binds FAP on the surface of CAFs and tumor cells to deliver the beta-particle emitting radioisotope 177Lu, resulting in DNA damage and cell death.vi,iv Compelling anti-tumor efficacy of 177Lu-FAP-2286 has been demonstrated in FAP-expressing preclinical tumor models.v

Following clearance of the INDs by FDA, the Phase 1/2 study LuMIERE is planned to start in the first half of 2021 to determine the dose of 177Lu-FAP-2286 to be used in Phase 2 development. The FAP-targeting imaging agent, 68Ga-FAP-2286, will be used to identify patients with FAP-positive tumors eligible for treatment with 177Lu-FAP-2286 in the study. Once the Phase 2 dose is determined, expansion cohorts will evaluate 177Lu-FAP-2286 and 68Ga-FAP-2286 in multiple tumor types.

About Peptide-Targeted Radionuclide Therapy

Peptide-targeted radionuclide therapy (PTRT) is a form of targeted radiotherapy that is emerging as a new treatment option for patients with cancervi. These therapies consist of a small amount of a radioactive isotope, known as a radionuclide, linked to cell-targeting peptide that binds to a cancer specific protein which selectively directs the radionuclide to tumors.v Following binding, the radionuclide warhead emits ionizing radiation causing DNA damage and cell death to neighboring tumor cells.vii

About FAP-2286

FAP-2286 is a preclinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two parts; a peptide that binds to FAP and a linker and site that can be used to attach radiation for imaging and therapeutic use. FAP is highly expressed in many epithelial cancers, including more than 90 percent of breast, lung, colorectal and pancreatic carcinomas.iii Clovis holds U.S. and global rights for FAP-2286 excluding Europe, Russia, Turkey and Israel. FAP-2286 is an unlicensed medical product.

About Clovis Oncology

Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring, developing and commercializing innovative anti-cancer agents in the U.S., Europe and additional international markets. Clovis Oncology targets development programs at specific subsets of cancer populations, and simultaneously develops, with partners, for those indications that require them, diagnostic tools intended to direct a compound in development to the population that is most likely to benefit from its use. Clovis Oncology is headquartered in Boulder, Colorado, with additional office locations in the U.S. and Europe. Please visit www.clovisoncology.com for more information.

i Garin-Chesa P et al. Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc Natl Acad Sci U S A. 1990;87(18):7235-9.
ii Park JE et al. Fibroblast activation protein, a dual specificity serine protease expressed in reactive human tumor stromal fibroblasts. J Biol Chem. 1999;274(51):36505-12.
iii Rettig WJ et al. Regulation and Heteromeric Structure of the Fibroblast Activation Protein in Normal and Transformed Cells of Mesenchymal and Neuroectodermal Origin. Cancer Res. 1993;53:3327–3335.
iv Yong KJ et al. Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET) Radiation Originating from 177Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenograpfts. Int. J. of Mol.Sci. 2016; 17: 736.
v Zboralski, D et al. Preclinical evaluation of FAP-2286, a peptide-targeted radionuclide therapy (PTRT) to fibroblast activation protein alpha (FAP). European Society for Medical Oncology (ESMO) Congress 2020. 18-22 September 2020. Madrid, Spain.
vi Grzmil M, Meisel A, Behé M., Schibli R. (2019) An Overview of Targeted Radiotherapy. In: Lewis J., Windhorst A., Zeglis B. (eds) Radiopharmaceutical Chemistry. Springer, Cham.
vii National Research Council 2007. Advancing Nuclear Medicine Through Innovation. Washington, DC: The National Academies Press. https://doi.org/10.17226/11985.

SOURCE: Clovis Oncology

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