Prostate Cancer Treatment 225Ac-J591 Is Approved By The FDA

(CTN News) – The FDA Prostate Cancer has granted clearance to an investigational new drug (IND) application for 225Ac-J591 (CONV01-α), a prostate-specific membrane antigen-targeted monoclonal antibody under investigation for the treatment of advanced prostate cancer, said Convergent Therapeutics.1

Convergent Therapeutics’ co-founder and CEO, Philip Kantoff, MD, said, “Receiving clearance for our IND is a big deal.”1 “While we’ve already treated well over 100 prostate cancer patients for investigator INDs, this is a big deal.

This new IND will give us a fast track to phase 3 studies and let us develop CONV01-α as a monotherapy and in combination with other prostate cancer therapies.”

Convergent plans to start phase 2 clinical trials in 2024 and a registration program in 2025.

2 225Ac-J591 showed preliminary efficacy and safety across all dose levels in 177Lu-naive metastatic castration-resistant prostate cancer (mCRPC) patients in a phase 1 multi-dose, dose escalation study (NCT04506567) at the American Association of Prostate Cancer Research Annual Meeting in Orlando, Florida in 2023.

Specifically, 21 patients (95%) in the study who had a prostate-specific antigen (PSA) change experienced a drop in PSA. There were 14 patients (67%) who experienced a 50% decline and 6 (27%) who experienced a 90% decline.

At baseline and 12 weeks, we collected circulating tumor cell (CTC) samples from 13 of 21 patients. There were 5 patients with unfavorable CTC counts at baseline (5/7.5 mL). The CTC count of 10 patients remained favorable or converted from unfavorable to favorable at 12 weeks, 6 patients experienced a 50% decline, and 5 patients went from detectable to undetectable.

Each dose level of 225Ac-J591 was well tolerated. A dose-limiting toxicity (DLT) was not observed in either cohort. Cohort 3 had two DLTs, one grade 2 and one grade 3. Low-grade, non-hematologic adverse events most commonly reported included fatigue (95%), xerostomia (69%), and nausea (57%).

Adding to the news release, Neil Bander, MD, Convergent’s CSO, stated, “In phase 1/2 trials, patients experienced minimal adverse effects.” A perfect biodistribution method ensures alpha particles are delivered without immediate and significant salivary gland toxicity or delayed renal toxicity.

CONV01-α’s design targets tumor-killing radiation to malignant cells while reducing off-tumor effects and dose, increasing treatment safety and efficacy.”

This study included 24 patients predominantly with 177Lu-naive mCRPC. There was a median age of 73.5 years. ECOG performance status 0 to 2 and progressive mCRPC after treatment with an AR pathway inhibitor and chemotherapy were requirements for inclusion in the study.

Identifying the phase 2 dose for DLTs was the primary objective of the study. An exploratory efficacy measure was PSA decline, radiographic response rate, biochemical/radiographic progression-free survival, overall survival, CTC change, and patient reported outcomes, as well as safety and correlates (plasma and tissue genomics, PSMA imaging).

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