On December 12, 2017 Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing tumor-targeted and immuno-oncology therapies based on its pioneering research in cancer epigenetics, reported that the first patient has been dosed in its Phase 1b/2 PROSTAR study of CPI-1205, a small-molecule inhibitor of EZH2, combined with enzalutamide or abiraterone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Constellation Pharmaceuticals, DEC 12, 2017, View Source [SID1234522670]).

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"The initiation of this combination study marks a significant milestone for the company as we execute on our goal to rapidly advance our pipeline of epigenetic therapeutics that have the potential to address difficult-to-treat cancers," said Adrian Senderowicz, M.D., senior vice president and chief medical officer of Constellation Pharmaceuticals. "Today’s announcement marks the first evaluation of CPI-1205 in solid tumors. We anticipate advancing CPI-1205 and other therapies from our EZH2 portfolio in additional solid tumor clinical trials in the future."

CPI-1205 is a potent, highly selective, first-generation small-molecule inhibitor of EZH2, a clinically-validated target in cancer. In multiple types of cancer, including mCRPC, EZH2 contributes to drug resistance over time by enhancing pro-tumor pathways, such as androgen receptor signaling. CPI-1205 has shown single-agent activity and synergistic activity with small-molecule androgen inhibitors in preclinical studies. CPI-1205 has also demonstrated single-agent clinical activity and a dose-dependent increase in exposure correlated to pharmacodynamic biomarkers during a clinical trial of CPI-1205 in selected lymphoma patients.

"There is a tremendous need for new, safe and effective medicines for advanced prostate cancer, especially for men with progressive mCRPC," said Mary-Ellen Taplin, M.D., Dana-Farber Cancer Institute and an investigator in the trial. "We look forward to learning how CPI-1205 may help overcome resistance mechanisms in mCRPC and extend response to therapy."

The Phase 1b portion of the PROSTAR study is designed to assess safety, pharmacokinetics, pharmacodynamics, as well as a recommended Phase 2 dose (RP2D) of CPI-1205 in combination with either enzalutamide (marketed as Xtandi by Astellas and Pfizer) or abiraterone acetate (marketed as Zytiga by Janssen), which are FDA-approved second-generation androgen inhibitors. The Phase 2 portion of the PROSTAR study will assess clinical activity and potential biomarkers to identify patient populations with higher clinical anti-tumor activity to CPI-1205.

About mCRPC

mCRPC is an advanced form of prostate cancer and is defined by disease progression despite treatment with androgen depletion therapy (ADT). mCRPC may present as one, or any combination of, a continuous rise in serum levels of prostate-specific antigen (PSA), progression of known metastases, or appearance of new metastases. Prognosis is associated with several factors, including the ability to perform certain daily activities and the presence of bone pain. Additional symptoms commonly include anemia (low healthy red blood cell levels), weight loss, fatigue, hypercoagulability (abnormal blood coagulation) and increased susceptibility to infection. mCRPC presents as a spectrum of disease ranging from patients without symptoms but rising PSA levels despite ADT, to patients with metastases and significant debilitation.

About CPI-1205

CPI-1205 is a therapeutic candidate from Constellation Pharmaceuticals’ EZH2 portfolio and is an inhibitor of Enhancer of Zeste Homolog 2 (EZH2). The function of EZH2 is to selectively suppress gene expression of several pro-cancer pathways that contribute to drug resistance.