• Updated LuMIERE Phase 1 data demonstrated a manageable safety profile with some preliminary evidence of anti-tumor activity
  • Eleven patients treated to date with ¹⁷⁷Lu-FAP-2286 up to 7.4 GBq/dose
  • No serious adverse events, treatment discontinuations, or deaths related to ¹⁷⁷Lu-FAP-2286 observed
  • Confirmed partial response (PR) in one patient who completed the maximum six administrations of ¹⁷⁷Lu-FAP-2286 in the 3.7 GBq dose cohort
    • Patient continues without disease progression or subsequent anti-cancer therapy more than twelve months after first dose
  • Stable disease (SD) in one heavily pretreated patient who completed four administrations of ¹⁷⁷Lu-FAP-2286 in the 5.55 GBq dose cohort
  • Recruitment of the 7.4 GBq dose cohort is ongoing
• FAP-2286 has shown high tumor uptake and good prolonged retention across a range of solid tumors

Clovis Oncology, Inc. (NASDAQ: CLVS) today announced an oral presentation at the 35^th 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). 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.

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 https://clovisoncology.com/pipeline/scientific-presentations/ 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.

About Clovis Oncology

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. Clovis Oncology is headquartered in Boulder, Colorado, with additional office locations in the US and Europe. Please visit www.clovisoncology.com for more information.

To the extent that statements contained in this press release are not descriptions of historical facts regarding Clovis Oncology, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Examples of forward-looking statements contained in this press release include, among others, statements of our intentions and expectations for our development and discovery programs, including the timing and pace of pre-clinical development, plans for clinical development, plans for additional applications of the FAP-2286 peptide, including potential indications, tumor types and combination trials, and regulatory plans with respect to FAP-2286. Such forward-looking statements involve substantial risks and uncertainties that could cause Clovis Oncology’s actual results, performance, or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in drug discovery and pre-clinical and clinical development, including the outcome of pre-clinical studies and clinical trials, whether initial results, findings or research will support future studies or development, whether future study results will be consistent with previous study findings or other results, including pre-clinical studies, results in named-patient or similar programs or clinical trials, whether additional studies not originally contemplated are determined to be necessary, the timing of initiation, enrollment and completion of planned studies and actions by the FDA, the EMA or other regulatory authorities regarding data required to support drug applications and whether to approve drug applications. Clovis Oncology undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the company in general, see Clovis Oncology’s Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and its other reports filed with the Securities and Exchange Commission.

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