Peptide-targeted radionuclide therapy ¹⁷⁷Lu-FAP-2286 produced a manageable safety profile and promising early efficacy findings in patients with advanced or metastatic tumors, according to data from the phase 1/2 LuMIERE clinical study (NCT04939610).1

In the study’s safety population (n = 11), treatment-emergent adverse effects (TEAEs) were primarily grade 1 and 2 across cohorts. Investigators reported no serious AEs, treatment discontinuations, or deaths related to ¹⁷⁷Lu-FAP-2286. Moreover, there was a confirmed partial response in 1 heavily pre-treated patient with pseudomyxoma peritonei of appendiceal origin; the patient completed 6 doses of 3.7 GBq and continued without disease progression or subsequent anticancer treatment for over 12 months following the first dose. One case of stable disease was also reported in 1 heavily pre-treated patient with gallbladder cancer who received 5.55 GBq of 177LU-FAP-2286 for 4 cycles of treatment. The initial data will also be used to determine the appropriate phase 2 dosing schedule.

“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,” Thomas A. Hope, MD, director of molecular therapy in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco, said in a press release on the data.2 “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.”

FAP-2286 is a cyclic peptide binding to FAP with high affinity. Preclinical research has highlighted the prolonged tumor retention of ¹⁷⁷Lu-FAP-2286.

In the study, investigators performed a PET/CT scan using the imaging agent ⁶⁸Ga-FAP-2286 in patients who were eligible for treatment with ¹⁷⁷Lu-FAP-2286. Dose levels for the study included 3.70 GBq, 5.55 GBq, 7.40 GBq, or 9.25 GBq of ¹⁷⁷Lu-FAP-2286. Treatment was administered on day 1 of each 6-week cycle of treatment for up to 6 cycles. The 7.40 GBq dose level is still enrolling.

Patients 18 years and older were eligible to participate in the LuMIERE study if they had confirmed refractory or progressive advanced or metastatic solid tumors following prior treatment with no alternative therapy options. Additional inclusion requirements included an ECOG performance status of 0 or 1, adequate organ function, and a life expectancy of at least 6 months. Measurable disease per RECIST criteria and no treatment previous systemic radionuclide therapy were also required.

The median age was 64 years (range, 27-71). The most frequently observed tumor types were colorectal carcinoma (27.3%) and pancreatic ductal adenocarcinoma (18.2%).

The primary end points of the study were safety and tolerability of ¹⁷⁷Lu-FAP-2286 along with determining the recommended phase 2 dose and schedule. Secondary outcome measures included the radiation dosimetry of ¹⁷⁷Lu-FAP-2286 as well as preliminary efficacy findings including investigator-assessed objective response rate. Other secondary end points included determining tumor uptake using ⁶⁸Ga-FAP-2286, and comparing the compound with ¹⁸F-FDG in CT/PET scans.

Grade 3 or higher TEAEs were observed in 5 patients (45.5%) in the safety population. Investigators reported a single occurrence of grade 3 or higher abdominal distension, cholangitis, hyponatremia, increased blood bilirubin, lymphopenia, and spinal compression fracture. The single event of lymphopenia was grade 4 and occurred in a patient treated at the 5.55 GBq dose level; this was considered a dose-limiting toxicity.

References

1. Hope TA, Aggarwal R, Goenka AH, et al. 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. Presented at: 35th Annual Congress of the European Association of Nuclear Medicine Congress; October 15-19, 2022; Barcelona, Spain. Abstract OP-355. Accessed October 18, 2022.

2. Clovis oncology highlights updated LuMIERE phase 1 data of targeted radiotherapy candidate FAP-2286 at the 35th Annual EANM Congress. News release. Clovis Oncology, Inc. October 17, 2022. Accessed October 18, 2022. https://bit.ly/3TwTUWY