Summary

• In MAGNITUDE, the phase 3 study evaluating the efficacy and safety of AKEEGA with prednisone compared to placebo/abiraterone acetate with prednisone (AAP) as first-line (L1) therapy in metastatic castration-resistant prostate cancer (mCRPC) for patients with certain homologous recombination repair (HRR) mutations, including BRCA1/2^1-4:
  • Germline and/or somatic HRR mutation status was determined using a required assay on plasma, tumor tissue, and/or saliva/whole blood samples for the following selected genes: ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, and PALB2.^2,5
  • Patients had to have a gene alteration detected by ≥1 assay to be eligible for the HRR+ cohort.²
  • Patients must have been tested by both tissue and plasma to be randomly assigned in the HRR- cohort.
• AMPLITUDE is a phase 3, randomized, double-blind, placebo-controlled, multicenter, global study evaluating the efficacy and safety of AKEEGA with prednisone plus androgen deprivation therapy (ADT) compared to matching oral placebo/abiraterone acetate with prednisone plus ADT in patients with deleterious germline or somatic homologous recombination repair (HRR) gene-altered metastatic castration-sensitive prostate cancer (mCSPC; N=696)^6,7:
  • Prescreening tests for HRR gene alterations included germline (blood, saliva), tissue (archival or recent biopsy), and circulating tumor DNA (plasma). Qualifying HRR gene alterations identified by local/commercial testing were potentially eligible.^8,9 
  • Patients had to have ≥1 deleterious germline or somatic HRR gene alteration to be eligible: BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, PALB2, RAD518, RAD54L.⁹
  • Key efficacy endpoint testing was conducted using a hierarchical graphical approach, first in the BRCA subgroup (BRCA1 or BRCA2 alterations), then HRR effector subgroup (ie, immediate effectors of HRR at DNA double-strand breaks [BRCA subgroup + BRIP1, PALB2, RAD51B, RAD54L]), and then all intention-to-treat (ITT) patients (HRR effectors subgroup + CDK12, CHEK2, and FANCA).⁷
• The following genetic tests were used in the MAGNITUDE study^2,5,10:
  • FoundationOne^® tumor tissue test (FoundationOne^®CDx)
  • Resolution Bioscience homologous recombination deficiency (HRD) plasma test for circulating tumor DNA (ctDNA)
  • AmoyDx blood and tissue assays
  • Invitae blood/saliva germline testing
  • Accredited local laboratory biomarker tests (with central review) demonstrating a pathogenic germline or somatic alteration listed in the study biomarker gene panel
• Results from an analysis that stratified efficacy by outcomes based on 2 different enrollment assays used to classify patients as HRR+, within the MAGNITUDE study, were reported.¹¹ 
  • The enrollment assays used were the FoundationOne^®CDx tissue assay and the Resolution Bioscience ctDx HRD™ (Resolution ctDx) plasma assay.
  • For HRR+ and BRCA1/2+ patients identified using either assay and treated with niraparib/AAP, radiographic progression-free survival (rPFS), overall survival (OS), time to initiation of cytotoxic chemotherapy (TCC), and time to symptomatic progression (TSP) were comparable.
• The US Food and Drug Administration (FDA) has approved FoundationOne^®CDx as well as FoundationOne^®Liquid CDx to be used as a companion diagnostic for AKEEGA.¹² Information on FDA-approved tests is available at: http://www.fda.gov/CompanionDiagnostics.
  • The clinical validity of plasma assay FoundationOne^®Liquid CDx testing to identify BRCA+ patients in the MAGNITUDE study has also been retrospectively evaluated and observed satisfactory concordance.¹³ 

FDA-approved COMPANION DIAGNOSTICS

Johnson & Johnson is not the owner or manufacturer of these tests, but we can share the following information:

FoundationOne^®CDx tissue biopsy test and FoundationOne^®Liquid CDx liquid biopsy test are FDA-approved for use as a companion diagnostic to identify patients with BRCA1/2 mutations who may benefit from treatment with AKEEGA in accordance with FDA approved labeling.¹²

For additional information regarding these tests, please consider the following options:

• Review the technical information (FDA label):
  • FoundationOne^®CDx: https://www.foundationmedicine.com/sites/default/files/media/documents/2024-06/f1cdx_technical_labeling_062124.pdf
  • FoundationOne^®Liquid CDx: https://www.foundationmedicine.com/sites/default/files/media/documents/2023-11/P190032_S011_F1LCDx%20Technical%20Label%5B76%5D.pdf
• Visit the Foundation Medicine, Inc. FoundationOne^®CDx website at: https://www.foundationmedicine.com/test/foundationone-cdx and FoundationOne^®Liquid CDx website at: https://www.foundationmedicine.com/test/foundationone-liquid-cdx for information about the tests as well as links to download a brochure and order tests.
• Visit https://www.foundationmedicine.com/contact for contact method options.

ADDITIONAL INFORMATION

Please refer to local labeling for additional guidance and considerations regarding approved companion diagnostic (CDx) tests.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 28 May 2025. Summarized in this response are relevant data pertaining to this topic in patients with prostate cancer.