All Authors:

Aaron Richard Hansen^1*, Aviral Singh², Stanley Ngai¹, Shyam M. Srinivas³, Amanda Macaraeg³, Jeffrey Y.C. Wong⁴, Tanya B. Dorff⁴, Howard Gurney⁵, Alison Yan Zhang⁵, Robert Dreicer⁶, Zhi Yang⁷, Peng Du⁷, Yüksel Ürün⁸, Özlem Küçük⁸, Pedro C. Barata⁹, Wei Xue¹⁰, Anne Robert¹¹, Denis V. Ferreira¹¹, Debora Barton¹¹, Giuseppe Cardaci²

¹Princess Alexandra Hospital, Brisbane, Australia; ²GenesisCare, Murdoch, Australia; ³University of California, Irvine, Orange, CA, USA; ⁴City of Hope, Duarte, CA, USA; ⁵Macquarie University, Sydney, NSW, Australia; ⁶University of Virginia School of Medicine, Charlottesville, VA, USA; ⁷Beijing Cancer Hospital, Beijing, China; ⁸Ankara University, Ankara, Turkey; ⁹University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA; ¹⁰Shanghai Renji Hospital, Shanghai, China; ¹¹Full-Life Technologies.

Presentation: European Society for Medical Oncology (ESMO) Congress, Madrid, Spain, October 23-27, 2026. Poster #2323eP.

Background:

Alpha-emitting [²²⁵Ac]Ac-FL-020 represents a new generation of PSMA-targeted RDCs with potential improvements in PK and pharmacodynamics compared with a beta-emitting RDC indicated for mCRPC.¹ Discovered using the UniRDC™ technology platform, [²²⁵Ac]Ac-FL-020 is designed to enhance tumor uptake while minimizing healthy tissue exposure, including to the salivary glands. ProTACT is an ongoing Phase 1, first-in-human, open-label, multicenter global study evaluating [²²⁵Ac]Ac-FL-020 in patients with mCRPC (NCT06492122). The FDA granted Fast Track Designation for [²²⁵Ac]Ac-FL-020 in mCRPC.

Aims and Objectives:

Primary objectives: RP2D (incidence of DLTs), safety, and tolerability of [²²⁵Ac]Ac-FL-020. Secondary objectives: Anti-tumor activity (based on PSA response, ORR, DCR, BOR per PCWG3/RECIST v1.1), PK profile, and dosimetry.

Methods:

Patient eligibility: Patients must have progressive mCRPC, with PSMA PET/CT-positive lesions, prior androgen receptor signaling inhibitors or CYP17 inhibitors, ≥1 prior taxane regimen (patients who declined taxane may be eligible), and adequate organ function. Exclusion criteria include extensive PSMA-negative disease, a superscan, untreated brain metastases, and prior radionuclide treatment other than [¹⁷⁷Lu]Lu-PSMA-617/I&T and Ra-223.

Study design: The study consists of dose escalation to determine the MTD and/or RP2D, and expansion to confirm safety of the RP2D and to evaluate preliminary antitumor activity. Patients receive [²²⁵Ac]Ac-FL-020 every 6 weeks for up to 6 cycles. Patients who benefit from treatment after 6 cycles may receive up to a maximum of 2 additional cycles. PK sampling is performed in all patients. Approximately 10 patients will receive [¹¹¹In]In-FL-020 and serial SPECT/CT for dosimetry prior to [²²⁵Ac]Ac-FL-020. The trial is enrolling patients in Australia, the United States, Turkey, and China.

Safety Results:

As of 9 Oct 2026, 39 patients have received [²²⁵Ac]Ac-FL-020 at up to 10 MBq per cycle. Of these, 15 remain on treatment, 4 completed ≥6 cycles (2 received additional cycles), and 20 discontinued (12 due to disease progression, 5 due to AEs, 2 due to investigator decision, and 1 withdrew consent).

No DLTs were observed up to the highest dose administered (10 MBq); the MTD was not reached. Grade ≥3 TEAEs occurred in 22 patients (56.4%). The most common (≥2 patients) Grade ≥3 TEAEs were lymphocyte count decreased (8 patients); anaemia (7 patients); platelet count decreased (5 patients); white blood cell count decreased (4 patients); neutrophil count decreased (3 patients); and decreased appetite (2 patients).

Dry mouth was reported in 32 patients (82.1%): 23 (59.0%) Grade 1 and 9 (23.1%) Grade 2. TESAEs occurred in 11 patients (28.2%); 3 patients (7.7%) had a TESAE considered related to [²²⁵Ac]Ac-FL-020. No individual TESAE occurred in more than 1 patient. There were 8 deaths on study, all of which were related to disease progression.

Efficacy Results:

As of 9 Oct 2026, PSA50 responses were observed in 15/17 (88.2%) evaluable patients receiving effective doses (6-8 MBq). Of these, 13/17 (76.5%) patients had PSA80 responses, and 8/17 (47.1%) went on to have PSA90 responses. PSA responses were observed at 6-8 MBq for 100% of patients naïve and 75% of patients exposed to prior ¹⁷⁷Lu.

One ¹⁷⁷Lu-naïve patient (8 MBq) had no post-baseline PSA measurement and is not evaluable. Data cutoff: 9 Oct 2026.

All 13 PSMA-PET-evaluable patients at 6-8 MBq had a decrease in SUV in subsequent scans. One patient (7 MBq) with best response to prior ¹⁷⁷Lu of PD had CR by PSMA-PET after 2 cycles. One patient (8 MBq) had near-complete disappearance of all tumors by PSMA-PET after 2 cycles and 97% decrease in PSA after 1 cycle. As of 9 Oct 2026, 6 patients have been enrolled and treated at 10 MBq; related PSA data are immature.

Conclusions:

[²²⁵Ac]Ac-FL-020 has been well tolerated, with no DLTs or treatment-related deaths. The observed safety profile thus far is consistent with expectations for this patient population receiving alpha therapies in a Phase 1 clinical trial.

Overall, 56.4% of patients had Grade ≥3 TEAEs (most commonly lymphocyte count decreased), 28.2% of patients had TESAEs (7.7% had TESAEs considered related to [²²⁵Ac]Ac-FL-020), and 12.8% discontinued due to AEs; all after receiving ≥2 cycles. Most discontinuations (60%) were due to disease progression, predominantly (75%) at dose levels <6 MBq. Dry mouth was reported in 82.1% of patients (59% Grade 1 and 23.1% Grade 2).

PSA50 responses were observed in 88.2% of evaluable patients who received 6-8 MBq, including 100% of ¹⁷⁷Lu-naïve and 75% of ¹⁷⁷Lu-exposed patients. PSA80 responses were observed at 8 MBq after 1 to 3 cycles and at 6 and 7 MBq after 2 to 3 cycles. PSA90 responses were observed at 8 MBq after 1 to 3 cycles, at 7 MBq after 2 cycles, and at 6 MBq after 4 to 5 cycles. This suggests superior anti-tumor activity with higher cumulative doses. By the data cutoff date, dose level 10 MBq enrolled 6 patients and was cleared by the DRC with no DLTs observed. These data support the continued development of [²²⁵Ac]Ac-FL-020.

Acknowledgements: Full-Life Technologies is the sponsor of this study. Wiesen Medical Writing provided editorial support.

Reference: 1. Sartor O, et al. N Engl J Med. 2021;385(12):1091–1103.