Janssen Abandons Regulatory Filing for Erleada (Apalutamide) + Zytiga (Abiraterone Acetate) + Prednisone Triple Combination in mCRPC

April 20, 2021 /Bio ValleyBIOON/ -- Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced that it will not seek regulatory approval based on the Phase 3 ACIS study. The study evaluated the efficacy and safety of Erleada® (apalutamide) in combination with Zytiga® (abiraterone acetate) and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) who were receiving androgen deprivation therapy (ADT) and had not previously received chemotherapy (chemotherapy-naive).

February 2021 in the United States ClinicalTumorData presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU 2021) showed that the study met its primary endpoint: compared with the placebo + Zytiga + prednisone arm (control group), the Erleada + Zytiga + prednisone arm (combination group) demonstrated a significant improvement in radiographic progression-free survival (rPFS), with a 31% reduction in the risk of radiographic progression or death. However, compared with the control group, the combination groupNo significant benefit was demonstrated for key secondary endpoints, including overall survival (OS).。

Kiran Patel, M.D., Vice President of Clinical Development for Solid Tumors at Janssen Research & Development, stated, “The safety results from the ACIS study were consistent with those from previous studies of Erleada and Zytiga plus prednisone, with no new safety signals observed. The study also evaluated a patient subgroup classified as luminal subtype by PAM50 assay, as well asTumor“The patient subgroup with average or high androgen receptor activity (a molecular hallmark of hormone sensitivity) yielded valuable scientific results and insights, warranting further investigation. These data will provide important guidance for our future initiatives, as we aim to build upon our leadership and commitment to deliver transformative therapies for patients with prostate cancer.”

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 presented at the ASCO-GU 2021 meeting showed that, compared with patients in the control group, those in the combination group had a median radiographic progression-free survival (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]). For 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, there were no statistically significant differences between the combination group and the control group.

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

The safety profile was consistent with previous studies of Erleada, and no new safety signals were observed. Grade 3/4 treatment-emergent adverse events (TEAEs) 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%). Based on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) total score, quality of life was comparable between the combination group and the treatment group.

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 prostateTumorZytiga blocks CYP17-mediated androgen production in tissues, where 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® (Zetga®, 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 those 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 male hormones, 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 globally 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 (Erleada®) 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 Provides Update on Phase 3 ACIS Study in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with ERLEADA (apalutamide) and ZYTIGA (abiraterone acetate) Plus Prednisone Combination