Pan-Cancer Analysis Suggests Fibroblast Activation Protein (FAP) is an Attractive Target for Peptide-Targeted Radionuclide Therapy with FAP-2286
Clovis Oncology (NASDAQ: CLVS) presented new nonclinical data on FAP-2286, a peptide-targeted radionuclide therapy, at the AACR-NCI-EORTC Virtual Conference from October 7-10, 2021. The study revealed high expression of fibroblast activating protein (FAP) in 9 out of 16 solid tumor types, including pancreatic and colon cancers. The Phase 1/2 LuMIERE trial is underway, focusing on patients with FAP-positive solid tumors. Approval for FAP-2286's clinical use could address significant cancer treatment gaps, potentially positioning Clovis as a leader in targeted radionuclide therapy.
- High expression of FAP in multiple tumor types, indicating a broad potential for FAP-2286.
- The ongoing Phase 1/2 LuMIERE clinical trial is actively enrolling patients, suggesting progress in clinical development.
- Significant correlation between FAP expression and FAP-2286 binding, reinforcing FAP as a promising cancer target.
- None.
- High expression of FAP, the target of radionuclide therapeutic development candidate FAP-2286, was observed across multiple tumor types and correlated with FAP-2286 binding
- Clovis Oncology’s clinical development of FAP-2286 is underway with the Phase 1/2 LuMIERE clinical trial now enrolling patients with FAP-positive solid tumors
“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,” said Dr.
To determine FAP protein expression in 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
The analysis also demonstrated that in most tumor types, FAP expression was predominantly 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.
Following are details of the Clovis-sponsored presentation:
Poster Number: LBA032 - Pan-Cancer Analysis of Fibroblast Activation Protein Alpha (FAP) Expression to Guide Tumor Selection for the Peptide-Targeted Radionuclide Therapy FAP-2286
Lead author:
Category: Radiotherapeutics
Date/Time:
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 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 US and global rights for FAP-2286 excluding
FAP-2286 is an unlicensed medical product.
About Targeted Radionuclide Therapy
Targeted radionuclide therapy is an emerging class of cancer therapeutics, which seeks 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.” Clovis, together with licensing partner 3B Pharmaceuticals, 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.
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
To the extent that statements contained in this press release are not descriptions of historical facts regarding
View source version on businesswire.com: https://www.businesswire.com/news/home/20211007005030/en/
Clovis Investor Contacts:
asussman@clovisoncology.com
or
bburkart@clovisoncology.com
Clovis Media Contacts:
US
clovismedia@clovisoncology.com
Jake.Davis@publicisresolute.com
Source:
FAQ
What is FAP-2286 and its significance in cancer therapy?
When was the data on FAP-2286 presented?
What types of tumors showed high FAP expression?
How does FAP-2286 work?