Positive preliminary data on FAP-2286 linked to the radionuclide lutetium-177 across a diverse array of adenocarcinomas was reported from the phase 1/2 LuMIERE trial.
FAP-2286 linked to the radionuclide lutetium-177 (177Lu-FAP-2286) yielded promising preliminary results when administered to a population of patients with different advanced solid tumors in the palliative setting, according to a press release on the phase 1/2 LuMIERE clinical study (NCT04939610) from Clovis Oncology.
According to investigators, 177Lu-FAP-2286 demonstrated a high uptake and a prolonged retention of the radiopeptide in primary and metastatic tumor lesions, resulting in high absorbed tumor doses in bone metastases (3.0 ± 2.7 Gy/GBq; range, 0.5-10.6). The whole-body effective doses were 0.07 ± 0.02 Gy/GBq (range, 0.04-0.1). Moreover, the mean absorbed doses for the kidneys was 1.0 ± 0.6 Gy/GBq (range, 0.4-2.0) and red marrow was 0.05 ± 0.02 Gy/GBq (range, 0.03-0.09).
“We believe the early clinical experience from named-patient use validates our plans to further investigate FAP-2286 as a therapeutic and imaging agent across a variety of solid tumor types,” Patrick J. Mahaffy, president and chief executive officer of Clovis Oncology, said in a press release. “We are very pleased to move FAP-2286 into formal clinical development with the recent initiation of the Phase 1/2 LuMIERE study of FAP-2286, a novel peptide-targeted radionuclide therapy in patients with solid tumors.”
The use of palliative 177Lu-FAP-2286 was assessed in 11 patients with progressive and metastatic adenocarcinomas of the pancreas, breast, rectum, and ovary following prior uptake on 68Ga-FAP-2286/-FAPI-04- PET/CT. FAP-2286 is a radionuclide therapy that targets fibroblast activation protein in those who have been diagnosed with advanced solid tumors.
To enroll on the LuMIERE study, patients needed to be 18 years or older and have consented to submission of archival tumor tissue. Moreover, it was necessary for patients to have adequate bone marrow, as well as hepatic and renal function. An ECOG performance status of 0 or 1, a life expectancy of at least 6 months, and measurable disease per RECIST 1.1 criteria were also required.
The primary objectives of phase 1 of the LuMIERE study are to determine the recommended phase 2 dose and scheduled for 177Lu-FAP-2286, as well as assessing the therapy’s safety profile, including adverse effects (AEs), serious AEs, and dose-limiting toxicities.
The data from a retrospective report published by Dr. Richard P. Baum and Dr. Harshad R. Kulkarniin in The Journal of Nuclear Medicine suggested that further research is warranted to better evaluate the safety and efficacy of 177Lu-FAP-2286 and determine which patient population may derive the most benefit from this treatment option.
Moreover, investigators noted that FAP-2286 labeled with gallium-68 will be used as an investigational imaging agent that can identify patients who are FAP-positive and determine if they are eligible for treatment with 177Lu-FAP-2286. FAP-2286 will be further evaluated in phase 2 expansion cohorts across multiple tumor types after the recommended phase 2 dose is determined.
Initial clinical experience of FAP-2286 in independent named patient use published In the journal Of nuclear medicine. News release. Clovis Oncology. June 28, 2021. Accessed August 23, 2021. https://tinyurl.com/mf9edsnn