Four in 10 adults with metastatic castration-resistant prostate cancer (mCRPC) and BRCA mutations respond to treatment with Zejula (niraparib), according to early results of an ongoing Phase 2 trial.
The GALAHAD study (NCT02854436), sponsored by Janssen, is testing 300 mg daily Zejula in patients whose disease worsened after treatment with next-generation androgen-receptor signaling therapies — a mainstay in the treatment of prostate cancer — and the chemotherapy docetaxel. All participants tested positive for a mutation in one of eight DNA repair genes.
Patient enrollment is ongoing at multiple locations. More information on study sites and contacts can be found here. A total of 120 patients have already been recruited, with an estimated total of 301.
As of the analysis cutoff date, the trial had enrolled 50 patients with a defect in both copies of a DNA repair pathway gene, 29 of whom had BRCA1/2 mutations — the most common in people with mCRPC — and 21 with alterations in other genes.
Zejula reduced tumor burden in 38% of those with BRCA1/2 mutations. It also led to a 62% composite response rate, defined by a reduction in tumor burden, the quantity of circulating tumor cells, or a 50% or greater decline in PSA levels.
Patients with non-BRCA1/2 mutations showed a 13% objective response rate and a 24% composite response rate.
Nearly half the patients have been on treatment for at least six months without disease progression.
The most frequent serious to life-threatening adverse events were blood-related, including low levels of red blood cells, platelets, neutrophils, or white blood cells. Other serious adverse events included lack of energy and strength and back pain.
The results were presented at the recent American Society of Clinical Oncology Genitourinary Cancers Symposium, in a poster titled, “Phase II study of niraparib in patients with metastatic castration-resistant prostate cancer (mCRPC) and biallelic DNA-repair gene defects (DRD): Preliminary results of GALAHAD.”
Zejula is an orally administered therapy that blocks the enzyme PARP with high selectivity. This enzyme helps repair damaged DNA. Blocking its effects in cancer cells leads to their death.
The treatment is currently marketed by Tesaro in the U.S., E.U. and Switzerland for the treatment of ovarian cancer. In 2016, Janssen and Tesaro entered a global (except Japan) collaboration and license agreement to develop the therapy in prostate cancer.
“These preliminary results suggest that PARP inhibition with niraparib may play an important role in the treatment of men with metastatic castration-resistant prostate cancer who have mutations in DNA repair genes,” Matthew R. Smith, MD, PhD, the lead investigator in GALAHAD, said in a press release.
Mentioning the unmet medical needs in this patient population, Smith, director of the Genitourinary Malignancies Program at the Massachusetts General Hospital Cancer Center and a professor of medicine at Harvard Medical School, added that the team is looking forward to “accumulating more evidence about the role of niraparib in this important setting.”
Margaret Yu, MD, Janssen Research & Development’s vice president of clinical development, prostate, said: “It is encouraging to see this promising response rate, since patients with this DNA repair pathway defect typically only have an objective response rate of less than 15 percent and a median progression-free survival of three months with currently available therapies.”
Progression-free survival refers to the length of time during or after treatment without cancer progression.
Yu added that the findings indicate that prospective biomarker testing could help define custom therapies for these patients in the future.
Besides GALAHAD, Janssen is also conducting the MAGNITUDE Phase 3 trial (NCT03748641), testing Zejula in combination with Zytiga (abiraterone acetate) and prednisone in adults with metastatic prostate cancer. In turn, the QUEST Phase 1/2 study (NCT03431350) tests Zejula combination therapies in patients with mCRPC.
Both MAGNITUDE and QUEST are enrolling participants. For more information, click on the trials’ identifiers.
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