PREDICT Phase 2 Trial: Three Treatment Arms Based on Genomic Profiles for Metastatic Prostate Cancer
Phase 2 Trial Stratifies Treatment Based on Genomics
PREDICT, a non-randomized, open-label Phase 2 clinical trial led by the Alliance for Clinical Trials in Oncology, enrolls 474 patients with metastatic castration-resistant prostate cancer (mCRPC). The trial began dosing on February 6, 2025, and is expected to complete on April 11, 2030. Patients are assigned to one of three treatment arms based on DNA and RNA analysis of their tumors and assessment by the Molecular Tumor Board (MTB), demonstrating the clinical utility of complex genomic patterns rather than a single biomarker.
EZH1/EZH2 Inhibition for Homogeneous Genotypes
Patients with RB1 loss, RB loss-of-function RNA signature, or neuroendocrine prostate cancer (NEPC) signature receive daily oral doses of valemetostat tosylate (Ezharmia) from Daiichi Sankyo (4568.T). This drug simultaneously inhibits histone methyltransferases EZH1 and EZH2, which suppress gene expression, and is in Phase 2 clinical trials for prostate cancer. The drug was approved by Japan's Ministry of Health, Labour and Welfare on September 26, 2022, for relapsed or refractory adult T-cell leukemia/lymphoma, but this approval was not for prostate cancer, making this study a pivotal trial for potential expansion into solid tumors.
Dual Chemotherapy for Aggressive Genotypes
Patients with two or more mutations in TP53, RB1, or PTEN, FANC mutations, or SLFN11 overexpression are assigned to a combination arm of carboplatin (Paraplatin) and cabazitaxel (Jevtana) from Sanofi (SNY). Carboplatin forms DNA crosslinks, and cabazitaxel stabilizes microtubules, inhibiting cell division, targeting aggressive tumors with both homogeneous genotypes and DNA damage vulnerability. The FDA approved Jevtana on June 17, 2010, for mCRPC after docetaxel therapy, but biomarker-driven carboplatin combination is the focus of this Phase 2 trial.
Precision Medicine Value Compared Directly to Standard of Care
The remaining patients, without defined trial mutations, receive a choice of abiraterone acetate (Zytiga) and CYP17A1 inhibition, enzalutamide (Xtandi) and androgen receptor inhibition, Jevtana, or lutetium Lu-177 vipivotide tetraxetan (Pluvicto) from Novartis (NVS), a PSMA-targeted radioligand, as selected by the physician. The FDA's initial approvals were Zytiga on April 28, 2011, Xtandi on August 31, 2012, and Pluvicto on March 23, 2022, all of which have shaped the treatment landscape for mCRPC. The global mCRPC market is projected to reach $21.04 billion in 2025, and if genomic assignment improves radiographic progression-free survival and response rates, it will have commercial implications for both diagnostic platforms and treatment selection algorithms.
From an investment perspective, PREDICT is a Phase 2 trial with 474 patients, testing whether Daiichi Sankyo's (4568.T) EZH1/EZH2 inhibitor, valemetostat, can expand beyond hematologic malignancies into prostate cancer. In the short term, the key value drivers are whether RB1, TP53, PTEN, FANC, and SLFN11 mutations, along with RNA signatures, actually differentiate treatment response, and the radiographic progression-free survival and objective response rates in each arm. Researchers can assess whether the combination of carboplatin and cabazitaxel, compared to the standard-of-care selection arm, demonstrates that a composite biomarker can identify a broader patient population than single BRCA or PSMA tests. The trial offers a new classification system that could compete with approved precision medicines such as Lynparza, Pluvicto, Akeega, and Rubraca in the $21.04 billion global mCRPC market in 2025; however, with a primary completion date of 2030, the clinical option value is prioritized over revenue contribution.
Source: ClinicalTrials.gov (api_ct)