Phase I/II trial of ¹⁷⁷ Lu-NYM032 for progressive metastatic castration-resistant prostate cancer.

Abstract

e17040 Background: Targeting Prostate-specific membrane antigen (PSMA) offers a promising therapeutic strategy for mCRPC. 177 Lu-NYM032 is a novel radionuclide drug conjugate that targets PSMA-expressing tumor cells. It was designed to deliver higher doses of radiation to neoplastic cells and lower doses of radiation to all other tissues than existing agents. The specific aims of this Phase I/II study (NCT06383052) include assessing the logistical feasibility, evaluating the safety, estimating the tolerability, and exploring the efficacy of 177 Lu-NYM032 in patients with PSMA-positive mCRPC. Methods: This single-center, single-arm, Phase I/II trial aims to recruit 40 men diagnosed with progressive mCRPC. The phase I dose-escalation was designed with a modified 3+3 model to determine the maximum tolerated dose (MTD) of 177 Lu-NYM032. Doses of 1.9, 3.7, 5.5, and 7.4 GBq were administered once every 6 weeks for up to 6 cycles. The MTD was defined as the highest dose level at which a dose-limiting toxicity (DLT) occurs in in fewer than 1/3 of participants, or no more than 2 of 6 participants. The phase II dose-expansion cohort will enroll an additional 30 participants to further evaluate the safety and anti-tumor efficacy of 177 Lu-NYM032 at the recommended Phase II dose (RP2D). Key eligibility criteria include confirmed PSMA-positive disease on 68 Ga-NYM032 PET/CT, no discordant lesions on 18 F-FDG PET/CT, prior progression following at least one potent androgen receptor (AR)-targeted therapy and docetaxel, or refusal/unfitness for chemotherapy. Selection criteria required subjects to have adequate organ function, an ECOG performance status 0-2, and no prior treatment with another radioisotope. Results: As of 1 January 2025, 11 Chinese participants with PSMA-positive mCRPC have been enrolled in the Phase I dose-escalation cohort. Patients were treated with 177 Lu-NYM032 at dose levels of 1.98 GBq (n = 1), 3.7 GBq (n = 4), 5.5 GBq (n = 3) and 7.4 GBq (n = 3). The treatments were well-tolerated, with all treatment-emergent adverse events (TEAEs) limited to Grade 1-2 except for one case of Grade 3 anemia. No DLTs had been reported. Among the 9 patients who completed 2 cycles of treatment, 7 (78%) experienced a reduction in PSA levels, with 6 (67%) demonstrating a greater than 50% decrease in PSA. Conclusions: Preliminary results from this ongoing Phase I/II trial indicate that 177 Lu-NYM032 is associated with manageable safety profile and demonstrates encouraging efficacy in patients with PSMA-positive mCRPC. These findings support the continued evaluation of 177 Lu-NYM032, with further studies needed to define the optimal dose and confirm its clinical benefit. The trial is ongoing, and additional data will be critical in determining the therapeutic potential of this novel radiolabeled drug. Research Sponsor: Norroy Bioscience Co., Ltd. Clinical trial information: NCT06383052 .