Janssen Announces Positive Phase 3 ACIS Trial Results for ERLEADA® (apalutamide) Plus ZYTIGA® (abiraterone acetate) in Metastatic Castration-Resistant Prostate Cancer

February 13, 2021 News /BioValleyBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently held at the U.S. clinical conference on February 11, 2021TumorResults from the Phase 3 ACIS study evaluating Erleada® (Erleada®, generic name: apalutamide) in combination with Zytiga® (Chinese brand name: Zytiga®, generic name: abiraterone acetate) for the treatment of prostate cancer were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU 2021).

Data show that the study met its primary endpoint: in patients with metastatic castration-resistant prostate cancer (mCRPC) who were chemotherapy-naïve and receiving androgen deprivation therapy (ADT), the Erleada + Zytiga + prednisone group (combination group) compared with the placebo + Zytiga + prednisone group (control group)Radiographic progression-free survival (rPFS) was significantly improved, with a 31% reduction in the risk of radiographic progression or death.

ACIS is a randomized, double-blind, placebo-controlled phase 3 study conducted in 982 patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) receiving androgen deprivation therapy (ADT). In the study, these patients were randomly assigned to receive either Erleada + Zytiga + prednisone (combination group) or placebo + Zytiga + prednisone (control group). The primary endpoint was radiographic progression-free survival (rPFS), and secondary endpoints included overall survival (OS), time to initiation of long-term opioid use, time to initiation of cytotoxic chemotherapy, and time to pain progression.

Preliminary efficacy analysis showed that, compared with patients in the control group, those in the combination group had a median rPFS prolonged by 6 months (22.6 vs. 16.6 months; HR=0.69 [95% CI: 0.58–0.83]; p<0.0001). The hazard ratio for radiographic progression or death assessed by blinded independent central review (BICR) was 0.864 [95% CI: 0.718–1.040]. According to the latest analysis with a median follow-up of 54.8 months, the risk of radiographic progression or death in the combination group was reduced by 30% compared with the control group (median rPFS: 24 months vs. 16.6 months; HR=0.70 [95% CI: 0.60–0.83]). There were no statistically significant differences between the combination group and the control group in secondary endpoints, including overall survival (OS), time to initiation of cytotoxic chemotherapy, time to initiation of long-term opioid use, and time to pain progression.

The overall ACIS study population exhibited heterogeneity in androgen receptor (AR) resistance and sensitivity markers. Data from prespecified analyses showed that patients aged ≥75 years, those with visceral metastases, those classified as luminal subtype by the PAM50 assay, and those with average or high AR activity (molecular features indicative of hormone sensitivity)TumorPatients may derive clinical benefit from the combination therapy of Erleada + Zytiga + prednisone, as revealed by the rPFS and OS outcomes in these patient subgroups.

Safety analysis was consistent with previous studies of Erleada, and no new safety signals were observed. Treatment-emergent adverse events (TEAEs) of Grade 3/4 occurred in 63.3% of patients in the combination group and 56.2% of patients in the control group. The more frequently occurring Grade 3/4 TEAEs in the combination and control groups included fatigue (4.7% vs 3.9%),Hypertension(20.6% vs 12.5%), falls (3.3% vs 0.6%), rash (4.5% vs 0.4%), cardiac disorders (9% vs 5.7%), fractures and osteoporosis (4.1% vs 1.4%), and seizures (0.2% vs 0%). According to the Functional Assessment of Cancer Therapy–Prostate (FACT-P) Total score, quality of life was comparable between the combination group and the treatment group.

Prostate Cancer (Image source: hopkinsmedicine.org)

Principal Investigator of the ACIS Study, Memorial Sloan Kettering Cancer CenterTumorMedical oncologist Dana Rathkopf stated, “Data from the ACIS study demonstrate a significant improvement in radiographic progression-free survival (rPFS) with the combination of Erleada, Zytiga, and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). Insights into the differential benefits observed in specific patient subgroups receiving the combination therapy warrant further evaluation.”

Dr. Craig Tendler, Vice President of Late-Stage Development and Global Medical Affairs in Oncology at Janssen Research & Development, stated, “The results of the ACIS study demonstrate the potential role of combination therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) and highlight the importance for prostate cancer patients, particularly those with low androgen receptor (AR) activityTumor“The medical needs of patients remain unmet. As we strive to advance the science and treatment of prostate cancer, these findings will inform our research efforts in developing novel approaches and combination therapies to improve outcomes for these patients.”

Zytiga (abiraterone acetate) is an oral medication that is converted in the body to abiraterone, an inhibitor of androgen biosynthesis in the testes, adrenal glands, and prostate.TumorZytiga blocks CYP17-mediated androgen production in tissues, and androgens can stimulate the growth of prostate cancer cells. Zytiga was approved by the U.S. FDA in April 2011 and by the European Commission (EC) in September 2011, in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). Additionally, Zytiga received EC approval in November 2017 and U.S.FDAApproved for the treatment of patients with high-risk metastatic castration-sensitive prostate cancer (mCSPC). Since its initial approval in 2011, the drug has been approved in more than 100 countries worldwide, and over 500,000 patients globally have received treatment with Zytiga.

In China, Zytiga® (Zelga®, abiraterone acetate) was approved in 2015 and 2018, respectively, for use in combination with prednisone or prednisolone to treat: (1) metastatic castration-resistant prostate cancer (mCRPC); (2) newlyDiagnosishigh-risk metastatic hormone-sensitive prostate cancer (mHSPC), including patients who have not received hormone therapy or have received hormone therapy for no more than 3 months.

Erleada (apalutamide) is a next-generation androgen receptor (AR) inhibitor that helps block the activity of androgens (such as testosterone), thereby delaying disease progression. In the United States, Erleada received its initial FDA approval in February 2018 for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC) at high risk of metastasis. This approval made Erleada the first drug worldwide for the treatment of nmCRPC. In September 2019,FDAApproval of a new indication for Erleada for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC).

In China, Erleada (ANSENKE®) received accelerated approval in September 2019 for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC) at high risk of metastasis, and was approved in August 2020 for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC). Notably, both indications were granted priority review status. (Bioon.com)

Original Source: Janssen Presents Results from Phase 3 ACIS Study in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with ERLEADA® (apalutamide) and ZYTIGA® (abiraterone acetate) Combination