Combo Shows Promise in High-Risk nmCRPC

Treatment with radiolabeled J591 plus ketoconazole and hydrocortisone may delay time to metastasis in patients with high-risk, non-metastatic castration-resistant prostate cancer (nmCRPC), according to researchers.

The combination produced a biochemical response in high-risk nmCRPC patients in a phase 2 trial. In addition, there was a numeric, but not significant, improvement in metastasis-free survival (MFS) when J591 was radiolabeled with ¹⁷⁷Lutetium (¹⁷⁷Lu) rather than ¹¹¹Indium (¹¹¹In).

These results were presented at the 2023 ASCO Genitourinary Cancers Symposium by Scott T. Tagawa, MD, of Weill Cornell Medicine/New York-Presbyterian Hospital in New York, New York.

The phase 2 trial (ClinicalTrials.gov Identifier: NCT00859781) included 55 patients with high-risk nmCRPC. At baseline, the median age was 68 years (range, 52-88), the median prostate-specific antigen (PSA) level was 8.0 ng/mL (range, 1-78), and the median PSA doubling time was 3 months (range, 0.87-7.85). Most patients (75%) had undergone prostatectomy, 22% had primary radiation, and 22% had local salvage therapy.

Study treatment consisted of a minimum 4 week lead-in with ketoconazole at 400 mg 3 times a day and hydrocortisone at 20 mg in the morning and 10 mg in the evening. Patients also received a single infusion of J591, an anti-prostate-specific membrane antigen antibody, radiolabeled with ¹⁷⁷Lu or ¹¹¹In.

In the intent-to-treat population (n=46), the incidence of metastasis at 18 months was 50% with ¹⁷⁷Lu-J591 and 76% with ¹¹¹In-J591 (P =.066). The median MFS was 23.8 months and 20.8 months, respectively.

The median biochemical progression-free survival was 18.67 months with ¹⁷⁷Lu-J591 and 8.87 months with ¹¹¹In-J591. There was a confirmed greater than 50% PSA decline in 82% of patients treated with ¹⁷⁷Lu-J591 and 71% of those treated with ¹¹¹In-J591.

Grade 3 or higher hematologic adverse events (AEs) that were more common with ¹⁷⁷Lu-J591 than with ¹¹¹In-J591 included neutropenia (57% vs 11%) and thrombocytopenia (77% vs 11%). Grade 3 or higher non-hematologic AEs that were less common with ¹⁷⁷Lu-J591 than with ¹¹¹In-J591 included abdominal pain (0 vs 11%), ALT increase (3.3% vs 22%), and diarrhea (0 vs 22%).

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Tagawa ST, Thomas C, Adra N, et al. Randomized, double-blinded phase II study of ketoconazole (keto), hydrocortisone (HC), and anti-PSMA antibody J591 labeled with ¹⁷⁷Lu or ¹¹¹In in patients (pts) with high-risk non-metastatic (met) castration-resistant prostate cancer (M0 CRPC). Presented at ASCO GU 2023. February 16-18, 2023. Abstract LBA21.

This article originally appeared on Cancer Therapy Advisor