On October 17, 2022 Clovis Oncology, Inc. (NASDAQ: CLVS) reported an oral presentation at the 35th Annual European Association of Nuclear Medicine Congress (EANM) detailing updated Phase 1 data from the Clovis Oncology-sponsored Phase 1/2 LuMIERE clinical study (NCT04939610) investigating the safety, pharmacokinetics, dosimetry, and preliminary anti-tumor activity of its targeted radiotherapy candidate, FAP-2286 labeled with lutetium-177 (177Lu-FAP-2286) (Press release, Clovis Oncology, OCT 17, 2022, View Source [SID1234622049]). Overall, in eleven patients treated in the first three dose cohorts, 177Lu-FAP-2286 demonstrated a manageable safety profile and encouraging evidence of anti-tumor activity, including previously reported confirmed partial response (PR) per RECIST in one patient and an additional patient with RECIST stable disease (SD) through cycle four of treatment. This dataset will be presented in an oral presentation by Thomas A. Hope, M.D., Director of Molecular Therapy in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco (UCSF), and principal investigator of the LuMIERE trial.
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FAP-2286 targets fibroblast activation protein (FAP), a promising theranostic target with expression across many tumor types. FAP-2286 is the first peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting FAP to enter clinical development and is the lead candidate in Clovis Oncology’s targeted radionuclide therapy (TRT) development program. The Phase 1 portion of the LuMIERE study is evaluating the safety of the investigational therapeutic agent 177Lu-FAP-2286 to identify the recommended Phase 2 dose and schedule. The safety and tumor uptake of the imaging agent 68Ga-FAP-2286 is also being evaluated, with plans for Phase 2 expansion cohorts in multiple tumor types to initiate in Q1 2023.
"The LuMIERE trial is the first prospective trial of a FAP peptide targeted radionuclide therapy and is currently in the dose escalation phase. To date we have not seen evidence of significant associated toxicities that would limit therapy, and have seen some evidence of early efficacy," said Thomas A. Hope, M.D., Director of Molecular Therapy in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco (UCSF), and principal investigator of the LuMIERE trial. "We are excited about these results and the fact that FAP is expressed across a number of tumor types, and we look forward to seeing the future results."
Updated results from the Phase 1 portion of the ongoing Phase 1/2 LuMIERE study found treatment-emergent adverse events (TEAEs) were mostly Grade 1 and 2 across cohorts. Data from the 7.4 GBq/dose cohort includes two patients who have completed the first cycle with enrollment ongoing. A dose-limiting toxicity of Grade 4 lymphopenia related to 177Lu-FAP-2286 was reported in one of six patients in the 5.55 GBq cohort; the patient had grade 2 lymphopenia at baseline. Overall, five patients (45.5%) had a Grade ≥3 TEAE, including abdominal distension (9.1%), cholangitis (9.1%), hyponatremia (9.1%), increased blood bilirubin (9.1%), and spinal compression fracture (9.1%); none were considered as related to 177Lu-FAP-2286.
There was good tumor uptake across a range of tumor types with prolonged tumor retention of 177Lu-FAP-2286 after dosing. Kidney and bone marrow radiation exposure observed appeared comparable to those reported in the literature for other lutetium-177 labeled radionuclide therapies with non-FAP targets.
A confirmed RECIST PR was reported in one heavily pre-treated patient in the 3.7 GBq dose cohort with pseudomyxoma peritonei of appendiceal origin, who completed the maximum six administrations of 177Lu-FAP-2286. The patient continues without disease progression or subsequent anti-cancer therapy more than twelve months after first dose. A RECIST best response of SD was reported in one heavily pre-treated patient in the 5.55 GBq dose cohort with gallbladder cancer who completed four administrations of 177Lu-FAP-2286 and remained stable without progressive disease through cycle four of treatment with subsequent progression.
"This presentation of updated data from the Phase 1/2 LuMIERE study continues to support the hypothesis that FAP-2286 gets to the tumor, stays in the tumor, and avoids off-target tissue, and these initial Phase 1 data further support the potential clinical utility of FAP-2286 as a targeted radionuclide therapy to treat a variety of advanced solid tumors," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We anticipate additional clinical data from the LuMIERE study to be presented at a medical conference in the first quarter of 2023."
Presentation of the initial LuMIERE Phase 1 data, titled "177Lu-FAP-2286 in Patients With Advanced or Metastatic Solid Tumors: Updated Data From a Phase 1/2 Study Investigating Safety, Pharmacokinetics, Dosimetry, and Preliminary Antitumor Activity (LuMIERE)" (Presentation #OP-355), is scheduled for Monday, October 17 at 9:45am CEST.
This presentation can also be viewed at View Source following presentation on October 17.
For more information about FAP-2286, targeted radionuclide therapy (TRT), or Clovis’ TRT development program, please visit targetedradiotherapy.com.
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. 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) is being 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 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 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 seeks to deliver radiation directly to the tumor while minimizing the 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.