A promising new therapy, 177Lu-NYM032, is showing potential in the fight against metastatic castration-resistant prostate cancer. This novel radionuclide drug conjugate, designed to deliver targeted radiation to prostate-specific membrane antigen (PSMA)-expressing tumor cells while sparing healthy tissues, is being evaluated in a phase I/II clinical trial (NCT06383052). Preliminary results from the phase I dose-escalation phase, conducted at a single center in China, indicate that 177Lu-NYM032 is well-tolerated and exhibits encouraging antitumor activity, offering hope for patients with limited treatment options.
177Lu-NYM032 binds lutetium-177, a beta-emitting radionuclide, to a PSMA-specific ligand, delivering precise radiation to cancer cells. Unlike existing agents, 177Lu-NYM032 is engineered to maximize radiation to tumors while minimizing exposure to healthy tissues, potentially improving both efficacy and safety.
The ongoing phase I/II trial aims to enroll 40 men with PSMA-positive mCRPC, confirmed by 68Ga-NYM032 PET/CT scans, who have progressed after at least one AR-targeted therapy and docetaxel (or are unfit for or refuse chemotherapy).
The phase I portion uses a modified 3+3 dose-escalation design to determine the maximum tolerated dose (MTD), testing doses of 1.9, 3.7, 5.5, and 7.4 GBq administered every 6 weeks for up to six cycles. The MTD is defined as the highest dose with dose-limiting toxicities (DLTs) in fewer than one-third of participants or no more than two of six. Key eligibility criteria include adequate organ function, an ECOG performance status of 0–2, no discordant lesions on 18F-FDG PET/CT, and no prior radioisotope therapy. The phase II dose-expansion cohort will recruit an additional 30 patients to further assess safety and efficacy at the recommended phase II dose (RP2D).
As of January 1, 2025, 11 Chinese patients have been enrolled in the phase I dose-escalation cohort, receiving 177Lu-NYM032 at doses of 1.98 GBq (1 patient), 3.7 GBq (4 patients), 5.5 GBq (3 patients), and 7.4 GBq (3 patients). The treatment has been well-tolerated, with all treatment-emergent adverse events (TEAEs) limited to mild or moderate (grade 1–2) except for one case of grade 3 anemia.
Notably, no DLTs have been reported, suggesting a favorable safety profile even at the highest dose tested. Among the nine patients who completed two treatment cycles, seven (78%) experienced a reduction in prostate-specific antigen (PSA) levels, a key indicator of tumor response. Impressively, six of these patients (67%) achieved a PSA decline of 50% or greater, highlighting the therapy’s potential to control cancer growth in this heavily pre-treated population.
The trial’s single-arm, single-center design and focus on a Chinese population provide valuable initial data but highlight the need for broader studies to confirm efficacy across diverse groups.