Pan-Tumor IHC Screen Suggests FAP Target is Attractive for PTRT
A pan-tumor IHC screen identified high fibroblast activating protein (FAP) expression in multiple tumor types that correlated with in vitro FAP-2286 binding, implying that FAP is an attractive target for peptide-targeted radionuclide therapy (PTRT).
The analysis, conducted by Clovis Oncology, Inc. with its partner 3B Pharmaceuticals GmbH, measured FAP expression in multiple tumor types using immunohistochemistry (IHC) as well as the correlation between FAP expression by IHC and in vitro binding of FAP-2286, Clovis’ PTRT clinical development candidate that targets FAP. Clovis revealed that the nonclinical data describing the expression of FAP in a variety of solid tumor types will be presented during the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics, taking place October 7-10, 2021.
Dr. Thomas Harding, Executive Vice President and Chief Scientific Officer of Clovis Oncology stated:
“We believe these findings across multiple solid tumor types demonstrate the importance of FAP as a cancer target and underscore the potential for 177Lu-FAP-2286 to treat patients with FAP-expressing tumors. These provide additional validation for our ongoing Phase 1/2 LuMIERE clinical trial of FAP-2286, the first peptide-targeted radionuclide therapeutic in clinical development targeting FAP, and support investigation of FAP-2286 in a broad number of cancer indications. This is representative of our commitment to emerge as a leader in targeted radionuclide therapy by developing innovative radiotherapies such as FAP-2286 for patients with hard-to-treat cancers.”
To determine FAP protein expression across different tumor types, a pan-tumor IHC screen was performed that included 360 samples representing 16 different tumor types. For this analysis, high FAP expression was defined as an overall H-score ≥30 in more than 30% of the samples analyzed in a given tumor type.
The IHC screen showed high FAP expression in nine of the 16 solid tumor types evaluated, including pancreatic ductal adenocarcinoma, cancer of unknown primary, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non–small cell lung, and squamous head and neck cancers. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade.
The analysis has also showcased that in the majority of tumor types, FAP expression was mostly localized to the stroma surrounding the tumor cells within the tumor microenvironment. FAP expression in tumor cells was also observed: in cancers of mesenchymal origin, such as sarcoma and mesothelioma, tumor-cell expression was common, consistent, and strong; in cancers of epithelial origin, tumor-cell FAP expression was rare and, when present, appeared weaker than in the adjacent stroma.
A significant correlation was seen between FAP expression observed by IHC and in vitro FAP-2286 binding as determined by autoradiography, suggesting that FAP is an attractive target for PTRT in a wide array of tumor types.
The presentation and accompanying poster can also be viewed at: https://clovisoncology.com/pipeline/scientific-presentations/
For more information about FAP-2286, Targeted Radionuclide Therapy (TRT), or Clovis’ TRT development program CLICK HERE.
About the investigational FAP-2286
FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use. High FAP expression has been shown in pancreatic ductal adenocarcinoma, cancer of unknown primary, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non–small cell lung, and squamous head and neck cancers. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade. Clovis holds the United States and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel. FAP-2286 is an unlicensed medical product.
About Targeted Radionuclide Therapy
Targeted radionuclide therapy is an emerging class of cancer therapeutics, which aims to deliver radiation directly to the tumor while minimizing delivery of radiation to normal tissue. Targeted radionuclides are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as “theranostics.”
About the LuMIERE Clinical Study
LuMIERE is a Phase 1/2 study evaluating FAP-2286 as a peptide-targeted radionuclide therapy (PTRT) targeting fibroblast activation protein, or FAP, in patients with advanced solid tumors (NCT04939610). The Phase 1 portion of the LuMIERE study is evaluating the safety of the investigational therapeutic agent and will identify the recommended Phase 2 dose and schedule of lutetium-177 labeled FAP-2286 (177Lu-FAP-2286). FAP-2286 labeled with gallium-68 (68Ga-FAP-2286) will be utilized as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment with the therapeutic agent. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types.
About Clovis Oncology
Headquartered in Colorado, Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring, developing, and commercializing innovative anti-cancer agents in the US, 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.
Together with licensing partner 3B Pharmaceuticals, Clovis, is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds.
Please visit www.clovisoncology.com for more information.