Initial results from Phase 3 MAGNITUDE study, to be featured in a late-breaking oral presentation at ASCO GU, highlight subset of patients with mCRPC most likely to benefit from treatment
The Janssen Pharmaceutical Companies of Johnson & Johnson today announced initial results from the Phase 3 MAGNITUDE study evaluating the investigational use of niraparib, a selective poly-ADP ribose polymerase (PARP) inhibitor, in combination with abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) with or without specific homologous recombination repair (HRR) gene alterations. At the final analysis for radiographic progression-free survival (rPFS), the treatment combination of niraparib and abiraterone acetate plus prednisone demonstrated a statistically significant improvement in patients with HRR gene alterations. Results will be featured in a late-breaking oral presentation (Abstract #12; Oral Abstract Session A) at the American Society of Clinical Oncology’s Genitourinary (ASCO GU) Cancers Symposium, taking place in San Francisco and virtually from February 17-19, 2022.
MAGNITUDE (NCT03748641) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of the combination of niraparib and abiraterone acetate plus prednisone as a first-line therapy in patients with mCRPC. The MAGNITUDE study was intentionally designed with two independent cohorts to assess treatment effect in patients with and without HRR gene alterations (including ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2 alterations) versus standard of care. The cohort of patients with prospectively-identified HRR gene alterations enrolled 423 patients, with patients randomized to receive the combination of niraparib and abiraterone acetate plus prednisone (combination arm [n=212]) or placebo and abiraterone acetate plus prednisone (control arm [n=211]). At 18.6-month median follow-up, patients in the combination arm of the cohort with HRR gene alterations showed a significant improvement in rPFS, with a reduction in the risk of progression or death of 27 percent (hazard ratio [HR] 0.73; p=0.022). This improvement was most pronounced in patients with BRCA1/2 gene alterations, where a 47 percent risk reduction was observed for rPFS (HR 0.53; p=0.001), as analyzed by blinded independent central review (BICR).
“When choosing a treatment plan for patients with prostate cancer, physicians must consider individual needs, particularly for patients with mCRPC with HRR gene alterations who face a poor prognosis,” said Dr. Kim Chi, Medical Oncologist at BC Cancer – Vancouver and principal investigator of the MAGNITUDE study.* “The MAGNITUDE data provide important context about the subgroup of patients with prostate cancer who may benefit from treatment with niraparib in combination with abiraterone acetate plus prednisone in the first-line setting, as well as those who may be better served by other treatment options.”
“These data suggest clinically meaningful improvements in outcomes in patients with prostate with HRR gene alterations who may derive benefit from this combination regimen, highlighting the importance of biomarkers to guide the patient selection process,” said Mary Guckert, RN, MSN, Vice President, Development Leader, Prostate Cancer, Janssen Research & Development, LLC. “The design of this trial aligns with the real-world setting as it includes patients with prostate cancer who were able to start first-line standard of care treatment, while awaiting HRR biomarker results, and shows the need to prospectively test for and identify patients most likey to benefit from the combination of niraparib and abiraterone acetate with prednisone.”
The observed safety profile of the combination of niraparib and abiraterone acetate plus prednisone was consistent with the known safety profile of each agent. Of the patients with HRR gene alterations, 67 percent experienced Grade 3 adverse events (AEs) and 46.4 percent experienced Grade 4 AEs, largely driven by anemia and fatigue. Discontinuation rates for the combination arm and control arm were 10.8 percent and 4.7 percent respectively. The combination of niraparib and abiraterone acetate plus prednisone also maintained overall quality of life in comparison with placebo and abiraterone acetate plus prednisone as measured on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) scale.
Niraparib is an orally administered, selective poly-ADP ribose polymerase (PARP) inhibitor, that is currently being studied by Janssen for the treatment of patients with prostate cancer. Additional ongoing studies include the Phase 3 AMPLITUDE study evaluating the combination of niraparib and abiraterone acetate plus prednisone in a biomarker-selected patient population with metastatic castration-sensitive prostate cancer and QUEST, a Phase 1b/2 study of niraparib combination therapies for the treatment of mCRPC.
About Metastatic Castration-Resistant Prostate Cancer
Metastatic castration-resistant prostate cancer (mCRPC) characterizes cancer that no longer responds to androgen deprivation therapy and has spread to other parts of the body. The most common metastatic sites are bones, followed by lymph nodes, lungs and liver. Prostate cancer is the second most common cancer in men worldwide, behind lung cancer.2 More than one million men around the world are diagnosed with prostate cancer each year. Patients with mCRPC and HRR gene alterations have a worse prognosis than those without HRR alterations.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology and Pulmonary Hypertension.