ESMO 2022: Efficacy and Safety of 177Lu-PNT2002 Prostate-Specific Membrane Antigen (PSMA) Therapy in Metastatic Castration Resistant Prostate Cancer (mCRPC): Initial Results from SPLASH

(UroToday.com) In the Prostate Cancer poster session of the European Society for Medical Oncology (ESMO) Annual Congress, Dr. Aaron Hansen presented the first, preliminary results of the SPLASH trial assessing the radioligand 177Lu-PNT2002 (also known as 177Lu-PSMA I&T) in PSMA-positive patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC) who progressed after treatment with androgen receptor axis-targeted therapy (ARAT). This first analysis presents the lead-in component of the phase 3 SPLASH trial.

SPLASH is a multi-national, open-label study that commenced with a 27-patient lead-in prior to the randomized trial. In SPLASH, the authors enrolled patients with tumors exhibiting high-PSMA uptake on positron emission tomography-computed tomography (PSMA PET/CT) per blinded independent central review (BICR) who had not received chemotherapy for CRPC but who had progressed on an ARAT. Finally, patients had to have adequate bone marrow and end-organ reserve.

Patients received up to four cycles of 177Lu-PNT2002 at 6.8 GBq per cycle every 8 weeks and were followed for key endpoints of radiographic progression-free survival (rPFS) per BICR, overall survival, PSA response, dosimetry, and safety.

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In this initial lead-in phase, 33 men underwent PSMA PET/CT to identify 27 (81.8%) eligible for treatment, of which 5 (15.2%) failed due to PSMA avidity criteria.

Among enrolled patient, included patients received a median 4 cycles of 177Lu-PNT2002, with a median dose of 6.9 (6.2-7.5) GBq/cycle. Six (22%) enrolled patients had previously received taxane chemotherapy for hormone-sensitive disease.

Based on a median rPFS follow-up of 9.2 months at data cut-off, median rPFS was 11.5 months with Kaplan Meier estimated 12-month rPFS of 44%. Notably, with a median follow-up of 11.7 months, median overall survival has not been reached.

One death was reported (non-treatment related) and 11 (42%) patients achieved a PSA50 response.

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In terms of tolerability, grade ≥3 treatment emergent adverse events (TEAEs) occurred in 8 (29.6%) patients, of which anaemia (3, 11.1%) and haematuria (3,11.1%) occurred in >10% of patients. Treatment-related TEAEs in > 10% patients included dry mouth (7, 25.9%), nausea (5, 18.5%), fatigue (5, 18.5%), haematuria and anaemia (3, 11.1%).

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Dr. Hansen thus concluded that, in mCRPC patients progressing following ARAT, 177Lu-PNT2002 was associated with a favorable rPFS and was well-tolerated. These data support the ongoing randomized portion of the SPLASH trial.

Presented by: Aaron R. Hansen, Medical Oncologist, Princess Margaret Cancer Centre at UHN, Associate Professor of Medicine, University of Toronto, Toronto, Canada

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.

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