Prostate cancer remains a significant health challenge for men, driving the need for innovative therapies, especially for advanced stages of the disease. Several Phase 3 trials are currently underway, exploring novel approaches to combat prostate cancer progression.
Candel Therapeutics Evaluates Oncolytic Virus Therapy
Candel Therapeutics is conducting the Phase 3 PrTK03 trial (NCT01436968) to determine the effectiveness of CAN-2409 (aglatimagene besadenovec) immunotherapy in conjunction with radiation therapy for patients with intermediate-high risk localized prostate cancer. The trial, expected to complete in December 2024, is a placebo-controlled study estimated to enroll 711 patients in the US and Puerto Rico, monitored every six months for five years. The primary endpoint is disease-free survival. Patients in the treatment arm receive CAN-2409, valacyclovir, radiation therapy, and potentially short-term androgen deprivation therapy (ADT), while the placebo group receives placebo, valacyclovir, radiation therapy, and potentially short-term ADT.
CAN-2409 delivers a gene directly to cancer cells using an inactivated herpetic virus, followed by anti-herpetic therapy with valacyclovir to kill the cells containing the gene. Dr. Robert Dreicer, deputy director of the University of Virginia Cancer Center, noted the trial's rationale but expressed cautious optimism.
Johnson & Johnson Investigates Akeega in Earlier Stage
Johnson & Johnson's AMPLITUDE study (NCT04497844) is assessing Akeega, a dual-action tablet combining niraparib (a PARP inhibitor) with abiraterone acetate, administered with prednisone, against abiraterone acetate and prednisone alone. This trial targets participants with deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-sensitive prostate cancer (mCSPC). The primary completion date is set for November 2024. The trial has enrolled 696 patients across 387 sites globally, with radiographic progression-free survival (rPFS) as the primary endpoint.
In the Phase III MAGNITUDE trial, BRCA-positive patients treated with Akeega plus prednisone showed a statistically significant 47% risk reduction in rPFS. However, patients without BRCA mutations did not exhibit as strong a benefit. The FDA has approved the combination therapy for BRCA-positive metastatic castration-resistant prostate cancer (mCRPC). Dr. Dreicer suggests that the data from MAGNITUDE indicates a greater benefit in patients with mutations in BRCA1 and BRCA2 genes.
Dr. Daniel Petrylak from Yale University is more hopeful for this study but has concerns about potential increased toxicity, such as myelodysplastic syndrome (MDS) or secondary leukemia, with earlier use of these drugs, emphasizing the importance of long-term analysis.
Pfizer Explores EZH2 Inhibition with Mevrometostat
Pfizer is conducting a Phase III trial (NCT06551324) investigating mevrometostat (PF-06821497) in men with mCRPC previously treated with abiraterone acetate. The MEVPRO-1 study aims to enroll 600 patients across 25 sites in the US, Australia, and Asia, with a primary completion date in December 2025. The primary endpoint is rPFS for up to two years. The treatment arm receives mevrometostat twice daily plus enzalutamide daily, while the active comparator arm receives either enzalutamide or docetaxel at the physician’s choice.
Mevrometostat inhibits enhancer of zeste homolog 2 (EZH2), a protein involved in prostate cancer cell growth. Dr. Petrylak highlights the trial's importance in testing a novel pathway, particularly for patients progressing on androgen receptor pathway inhibitors. He notes that EZH2, when mutated, can act as a co-activator for the androgen receptor, making it a potential target to overcome AR pathway resistance.
Biswajit Podder, PhD, oncology and hematology analyst for GlobalData, expresses concerns regarding the trial design, particularly the absence of a single-agent mevrometostat arm and the reintroduction of androgen therapy in patients who have already progressed on similar treatments.
