177Lu-rosopatamab tetraxetan (TLX591)

P3, N=430, Recruiting, Telix Pharmaceuticals (Innovations) Pty Limited | Not yet recruiting --> Recruiting

P3, N=430, Not yet recruiting, Telix Pharmaceuticals (Innovations) Pty Ltd

P3, N=392, Recruiting, Telix Pharmaceuticals (Innovations) Pty Ltd | Not yet recruiting --> Recruiting | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Jun 2025 --> Nov 2025

P2, N=5, Active, not recruiting, Telix Pharmaceuticals (Innovations) Pty Limited | Recruiting --> Active, not recruiting | N=50 --> 5 | Trial completion date: Jun 2025 --> Aug 2024

29 (58%) with prior >2 ARPI, 29 (58%) with >1 chemo, 14 (28%) with Ra-223, 2 (4%) with 177 Lu-J591... A single-cycle of fractionated-dose 177Lu-PSMA-617 is safe. Despite no pre-selection for PSMA expression, most had PSA decline with favorable PFS and OS compared to historical controls and similar to PSMA-selected targeted radionuclide studies administering multiple cycles in a less dose-intense approach.

P1, N=30, Completed, Telix International Pty Ltd | Recruiting --> Completed | N=50 --> 30 | Trial completion date: Sep 2024 --> Sep 2023 | Trial primary completion date: Mar 2024 --> Sep 2023

Eligible patients must have received prior therapy with either enzalutamide or abiraterone plus prednisone, and 1 line of prior taxane therapy or have refused or are ineligible for taxanes. Secondary endpoints include 5-year overall survival, tumor objective response rate, time to symptomatic skeletal event, progression free survival, and number of participants with treatment-related adverse events. Clinical trial information: NCT04876651.

The primary endpoints include the absorbed radiation dose of administered 177Lu-TLX591 to kidneys, liver, lungs, spleen, bone/red marrow, and salivary glands; tumour-to-healthy tissue ratios and residence times; and type, frequency, and severity of TEAEs. Clinical trial information: NCT04786847.

NLR provides prognostic information in the setting of patients with mCRPC receiving treatment with PSMA-TRT.

P1, N=50, Recruiting, Telix International Pty Ltd | Trial primary completion date: Mar 2023 --> Mar 2024

Median age 71 (IQR 66-77.5), PSA 57.3 ng/mL (21.3-294.9), 80 (44.4%) prior chemotherapy, 86 (47.7%) prior abiraterone or androgen receptor signaling inhibitor, 167 (92.8%) bone metastases, 141 (78.3%) nodal metastases, 113 (62.8%) CALGB high-risk group. 94 (52.2%) received 177Lu-J591, 51 (28.3%) 177Lu-PSMA-617, 28 (15.6%) 225Ac-J591, 7 (3.9%) 90Y-J591... For patients with mCRPC receiving PSMA TRT, NLR may have prognostic implications with higher NLR associating with lower likelihood of PSA response and shorter overall survival.

P1, N=50, Recruiting, Telix International Pty Ltd | Not yet recruiting --> Recruiting | Trial primary completion date: Dec 2022 --> Mar 2023

P2, N=50, Recruiting, Telix International Pty Ltd | Not yet recruiting --> Recruiting

SoC therapy will continue according to standard practice. Cohort 2: All further enrolled patients will receive two administrations of 76 mCi TLX591 for further evaluation of safety, tolerability and biodistribution, and efficacy in combination with SoC.

P1/2 | "29 (58%) with ≥2 prior ARPI, 29 (58%) chemo, 14 (28%) radium-223, 2 (4%) 177Lu-J591. A single-cycle of fractionated-dose 177Lu-PSMA-617 is safe. Despite no pre-selection for PSMA expression, most have post-treatment PSA decline with favorable biochemical and radiographic progression-free survival compared to historical non-PSMA controls and similar to PSMA-selected studies administering multiple cycles in a less dose-intense fashion."

177Lu-J591 demonstrated accurate targeting of known metastatic sites, based on post-treatment scintigraphy, in study populations that were not selected for PSMA expression, with evidence of dose-response and dose-limiting myelosuppression...A phase II randomized study of 177Lu-PSMA-617 showed a superior PSA50 response rate (66 vs 37%) over cabazitaxel in patients with docetaxel-pretreated, progressive mCRPC selected by PSMA and FDG PET/CT scans...The first randomized data with 177Lu-PSMA-617 (phase 2) have been presented, and the first phase 3 trial has completed accrual with radiographic progression-free and overall survival as dual primary endpoints. Multiple additional phase 3 trials of PSMA-TRT are starting and studies investigating optimal patient selection and combination therapy continue.

Single-agent anti-PSMA antibody J591 may lead to decline in CTC count, though the study did not meet its primary endpoint. A combination or maintenance approach might be preferable and is worthy of exploration.

38 (57%) received 177Lu-PSMA-617, 16 (24%) 177Lu-J591, 7 (11%) 225Ac-J591, and 5 (8%) both 177Lu-PSMA-617 and 177Lu-J591. AR resistance mutations and amplifications appear to result in poorer outcome following PSMA-TRT both in terms of PSA decline and overall survival. Genetic sequencing may inform responses to PSMA-based therapies, and prospective genomic panel testing is ongoing.Supported by: Weill Cornell Medicine, Prostate Cancer Foundation, Department of Defense, NIH

55% with at least 1 prior chemo regimen, 52% >2 prior ARPI, 27% with Ra223, 30% sip-T, 5% 177Lu-J591. A single cycle of up to 22.2 GBq of 177Lu-PSMA-617 is safe with fractionated (D1 & D15) dosing, with encouraging early efficacy signals in a population unselected for PSMA expression and improved quality of life and pain scores by validated PRO instruments. Clinical trial information: NCT03042468. Research Funding: Weill Cornell Medicine, Other Foundation, Other Government Agency, Pharmaceutical/Biotech Company, U.S. National Institutes of Health.

55% with at least 1 prior chemo regimen, 52% >2 prior ARPI, 27% with Ra223, 30% sip-T, 5% 177Lu-J591. A single cycle of up to 22.2 GBq of 177Lu-PSMA-617 is safe with fractionated (D1 & D15) dosing, with encouraging early efficacy signals in a population unselected for PSMA expression and improved quality of life and pain scores by validated PRO instruments. Clinical trial information: NCT03042468. Research Funding: Weill Cornell Medicine, Other Foundation, Other Government Agency, Pharmaceutical/Biotech Company, U.S. National Institutes of Health.