1400P - Efficacy and safety of 177Lu-PNT2002 prostate-specific membrane antigen (PSMA) therapy in metastatic castration resistant prostate cancer (mCRPC): Initial results from SPLASH

Background

Preliminary results of the SPLASH (NCT04647526) lead-in, a phase 3 study evaluating the PSMA targeted radioligand, ¹⁷⁷Lu-PNT2002 (also known as ¹⁷⁷Lu-PSMA I&T), in PSMA-positive patients with mCRPC who progressed after treatment with androgen receptor axis-targeted therapy (ARAT), are herein presented.

Methods

This multi-national, open-label study commenced with a 27-patient lead-in prior to the randomization. Patients were enrolled with tumors exhibiting high-PSMA uptake on positron emission tomography–computed tomography (PSMA PET/CT) per blinded independent central review (BICR), chemotherapy naïve for CRPC, progressing on an ARAT, and 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.

Results

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. Patients received a median 4 cycles of ¹⁷⁷Lu-PNT2002, with a median dose of 6.9 (6.2-7.5) GBq/cycle. Six (22%) patients who underwent treatment received a prior taxane for hormone-sensitive disease. Based on a median rPFS follow-up of 7.5 months at data cut-off, 21 (78%) remained event-free with a rPFS rate at 9 months of 75.4%. There was one death reported (non-treatment related) and 11 (42%) patients achieved a PSA50 response. 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%).

Conclusions

In mCRPC patients post-ARAT failure, ¹⁷⁷Lu-PNT2002 was associated with a favorable rPFS and was well-tolerated. Anti-neoplastic efficacy was exhibited based on PSA50 response. These results support the advancement of ¹⁷⁷Lu-PNT2002 to the randomized portion of the SPLASH registrational trial.

Clinical trial identification

NCT04647526.

Editorial acknowledgement

None

Legal entity responsible for the study

POINT Biopharma.

Funding

POINT Biopharma.

Disclosure

A.R. Hansen, R.F. Tutrone, M.M. Osman, E.S. Delpassand, L.T. Nordquist, B.L. Viglianti, J.M. Michalski, J. Beauregard, O.K. Oz, K. Courtney: Non-Financial Interests, Institutional, Principal Investigator: POINT Biopharma. S. Probst: Financial Interests, Personal, Invited Speaker: POINT Biopharma; Non-Financial Interests, Institutional, Principal Investigator: POINT Biopharma; Non-Financial Interests, Personal, Advisory Role: POINT Biopharma. J. Jensen: Financial Interests, Personal, Full or part-time Employment: POINT Biopharma; Financial Interests, Personal, Stocks/Shares: POINT Biopharma; Non-Financial Interests, Personal, Officer: POINT Biopharma; Non-Financial Interests, Personal, Proprietary Information: POINT Biopharma; Non-Financial Interests, Personal, Sponsor/Funding: POINT Biopharma; Non-Financial Interests, Personal, Leadership Role: POINT Biopharma. W. Wu: Financial Interests, Personal, Full or part-time Employment: POINT Biopharma; Financial Interests, Personal, Stocks/Shares: POINT Biopharma; Non-Financial Interests, Personal, Sponsor/Funding: POINT Biopharma. N. Fleshner: Financial Interests, Personal, Officer: POINT Biopharma; Financial Interests, Personal, Full or part-time Employment: POINT Biopharma; Financial Interests, Personal, Ownership Interest: POINT Biopharma; Financial Interests, Personal, Stocks/Shares: POINT Biopharma; Non-Financial Interests, Personal, Proprietary Information: POINT Biopharma; Non-Financial Interests, Personal, Sponsor/Funding: POINT Biopharma; Non-Financial Interests, Personal, Advisory Role: POINT Biopharma; Non-Financial Interests, Personal, Leadership Role: POINT Biopharma. O. Sartor: Non-Financial Interests, Institutional, Principal Investigator: POINT Biopharma; Financial Interests, Personal, Advisory Board: POINT Biopharma; Financial Interests, Personal, Stocks/Shares: POINT Biopharma; Financial Interests, Personal, Advisory Role: POINT Biopharma. K.N. Chi: Non-Financial Interests, Institutional, Principal Investigator: POINT Biopharma; Financial Interests, Personal, Advisory Role: POINT Biopharma; Financial Interests, Personal, Advisory Board: POINT Biopharma. S.T. Tagawa: Financial Interests, Personal, Advisory Board: Convergent Therapeutics, AIkido Pharma; Financial Interests, Personal, Other, Consultant: EMD Serono, Telix Pharma, Blue Earth Diagnostics, POINT Biopharma, Myovant, Bayer, 4D Pharma, Gilead, Pfizer, Janssen, Astellas, AbbVie, Novartis, Seagen, Clarity; Financial Interests, Personal, Stocks/Shares: AIkido Pharma; Financial Interests, Personal, Other, Patent co-inventor: Gilead; Financial Interests, Institutional, Invited Speaker: Medivation, Astellas, Janssen, Amgen, BMS, AstraZeneca, Bayer, Merck, Clovis, Seagen, Gilead, Novartis, POINT Biopharma, Clarity, Ambrx, Phosplatin.