LuPIN Program

(Lutetium-PSMA in Combination with Veyonda^®)

Veyonda^® combined with¹⁷⁷Lutetium-PSMA-617 (Lu-PSMA)

Objectives - to demonstrate that in late-stage prostate cancer:

• The immuno-oncology actions of Veyonda increase the proportion of men responding meaningfully to the radionuclide Lu-PSMA
• Veyonda in combination with Lu-PSMA increases the durability of the anti-cancer response

¹⁷⁷Lu-PSMA-617 is an intravenous radiopharmaceutical emerging as a promising new treatment in late-stage prostate cancer. The LuPIN study set out to explore whether adding Veyonda to ¹⁷⁷Lu-PSMA-617 would provide a meaningful response and lead to increased overall survival.

Phase 1b/2a study - complete

Veyonda combined with ¹⁷⁷Lutetium-PSMA-617 (Lu-PSMA), a radionuclide

An investigator-initiated Phase 1b/2a trial led by Professor Louise Emmett at St Vincent’s hospital in Sydney for the management of advanced prostate cancer that has stopped responding to hormonal or chemotherapy.

LuPIN involved 56 men with advanced mCRPC (19 patients had < 20 metastases; 37 > 20 metastases) whose disease had progressed following three lines of treatment (abiraterone/enzalutamide, docetaxel and cabazitaxel). The study tested three dosages of Veyonda^® – 400mg, 800mg and 1200 mg - with a constant Lu-PSMA dosage.

Interim data on the first 32 patients was first published in the peer-reviewed European Urology Oncology (Crumbaker et al, 2020)^[i]. At that stage results were highly encouraging with a high PSA response rate and a median overall survival of 17.1 months versus a 4.5-month median overall survival for a comparable patient population receiving standard chemotherapy.

The study is now complete and data on the full 56 patients was presented at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, a major medical conference, and published in the Journal of Nuclear Medicine in 2021.^[ii]

The results presented were:

High PSA response rate. 61% had a PSA reduction >50% and 86% had any PSA reduction

53% of men suffering moderate to strong pain associated with cancer reported a significant reduction in pain.

Progression free survival (PFS) of 7.5 months, and 5 of 56 men have not progressed

46% of men were able to complete the full 6 cycles of treatment without cancer progression

Median overall survival (mOS) of 19.7 months versus a 4.5-month median overall survival for a comparable patient population receiving standard chemotherapy.

A mOS of 19.7 months is particularly of note as the patients recruited had end-stage metastatic disease and their disease had progressed despite a number of prior treatment pathways.

There are multiple studies on similar patient populations that were treated with ¹⁷⁷Lu-PSMA-617 as a sole treatment; the LuPIN combination treatment incorporating Veyonda compares favourably with these studies.

The LuPIN mOS outcome of 19.7 months provides the best survival outcome when comparing to Lu-PSMA alone.

[i] Crumbaker M, Pathmanandavel S, Yam AO, Nguyen A, Ho B, Chan L, Ende JA, Rofe C, Kongrak K, Kwan EM, Azad AA, Sharma S, Pugh TJ, Danesh A, Keane J, Eu P, Joshua AM, Emmett L. Phase I/II Trial of the Combination of 177Lutetium Prostate specific Membrane Antigen 617 and Idronoxil (NOX66) in Men with End-stage Metastatic Castration-resistant Prostate Cancer (LuPIN). Eur Urol Oncol. 2020 Aug 2:S2588-9311(20)30093-6. doi: 10.1016/j.euo.2020.07.002. Epub ahead of print. PMID: 32758400. https://euoncology.europeanurology.com/article/S2588-9311(20)30093-6/fulltext

[ii] Pathmanandavel S, Crumbaker M, Yam AO, Nguyen A, Rofe C, Hovey E, Gedye C, Kwan EM, Hauser C, Azad AA, Eu P, Martin AJ, Joshua AM, Emmett L. 177Lutetium PSMA-617 and idronoxil (NOX66) in men with end-stage metastatic castrate-resistant prostate cancer (LuPIN): Patient outcomes and predictors of treatment response of a Phase I/II trial. J Nucl Med. 2021 Jul 29:jnumed.121.262552. https://doi.org/10.2967/jnumed.121.262552