On June 14, 2022, Clovis Oncology, Inc. (the “Company”)
announced initial Phase 1 data from the Company-sponsored Phase 1/2
LuMIERE clinical study (NCT04939610) investigating the safety,
pharmacokinetics, dosimetry, and preliminary antitumor activity of
its targeted radiotherapy candidate, FAP-2286 labelled with lutetium-177 (177Lu-FAP-2286). Overall, in
nine patients treated in the first two dose cohorts, 177Lu-FAP-2286 demonstrated a
manageable safety profile and encouraging evidence of activity,
including a confirmed RECIST partial response in one patient.
In addition, on June 14, 2022, the Company announced that
updated data from an investigator-initiated Phase 1 study of
FAP-2286 labelled with
gallium-68 (68Ga-FAP-2286) as a novel imaging
agent to identify metastatic cancer in patients with solid tumors
were presented (NCT04621435) in an oral presentation at the Society
of Nuclear Medicine & Molecular Imaging (SNMMI) Annual
Meeting 2022 in Vancouver, British Columbia.
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 the
Company’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 the fourth quarter of 2022.
Initial results from the Phase 1 portion of the ongoing Phase 1/2
LuMIERE study found treatment-emergent adverse events (TEAEs) to be
generally mild to moderate among the nine patients in the safety
population receiving 3.7 or 5.55 GBq/dose of the investigational
therapeutic agent 177Lu-FAP-2286. Three patients
(33.3%) had a Grade ≥3 TEAE of back pain (11.1%), abdominal
distension (11.1%), increased bilirubin (11.1%) and hyponatremia
(11.1%); none were judged as related to 177Lu-FAP-2286. There was one
serious adverse event (SAE) of back pain not related to
177Lu-FAP-2286. No dose-limiting
toxicities were observed in the 3.7 or 5.55 GBq cohorts (n=3
evaluable in each cohort).
At the two dose levels evaluated to date, organ dosimetry revealed
target organ exposure within the expected range to support
administration of multiple doses. There was tumor uptake across a
range of tumor types with prolonged tumor retention of 177Lu-FAP-2286 after dosing.
A confirmed RECIST partial response was reported in one heavily
pre-treated patient in the
3.7 GBq dose cohort with pseudomyxoma peritonei of appendiceal
origin who completed six administrations of 177Lu-FAP-2286. A decrease in
the level of the serum tumor marker carcinoembryonic antigen (CEA)
was also observed in the patient over the course of 177Lu-FAP-2286
Recruitment for the third dose cohort (7.4 GBq) is ongoing.
The Company expects to present additional clinical data from the
LuMIERE study at another nuclear medical meeting and initiating
Phase 2 expansion cohorts in multiple tumor types in the fourth
quarter of 2022.
The Company submitted to the FDA and EMA final overall survival
(OS) data in primary efficacy populations from our ARIEL3 trial,
the double-blind, multicenter clinical trial in which 564 patients
with recurrent epithelial ovarian, fallopian tube, or primary
peritoneal cancer who were in response to platinum-based
chemotherapy were randomized to receive Rubraca or placebo. In
the tBRCA population, the hazard ratio (HR) was 0.832 with a
nominal p-value of 0.3162;
in the HRD population, the HR was 1.005 with a nominal p-value of 0.9693 and in the
population, the HR was 0.995 with a nominal p-value of 0.9621. The Company has
submitted an abstract to present the full OS data from the ARIEL3
trial, including for the exploratory subgroups, at the Annual
Global Meeting of the International Gynecological Cancer Society
(IGCS) to be held in New York City from September 29 through
October 1, 2022.
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