Constellation doses first patient in phase 1 trial of CPI-0209 for cancer

Constellation Pharmaceuticals, a US clinical-stage biopharmaceutical company, has dosed the first patient in a Phase 1/2 clinical trial of CPI-0209, a second-generation EZH2 (enhancer of zeste homolog 2) inhibitor in cancer.

The Phase 1 dose-escalation phase of the clinical trial will assess the efficacy of CPI-0209 monotherapy in advanced, relapsed solid tumor patients.

With extended on-target residence time and increased potency, CPI-0209 is said to achieve complete target coverage for faster onset of action and robust anti-tumor activity in models of multiple cancer types.

Dr Patrick Trojer – chief scientific officer of Constellation Pharmaceuticals said: “We recognized that a best-in-class molecule with enhanced potency and residence time may help to access the full potential of EZH2 inhibition in cancer.

“We believe that CPI-0209 can deliver on this need, and we are eager to learn more about CPI-0209 in the clinic.

“We have seen impressive pre-clinical activity of CPI-0209 and are excited to take the first steps toward bringing CPI-0209 to patients.”

In vivo, once-daily treatment with CPI-0209 in bladder cell-line derived xenografts harboring ARID1A mutations achieved regression at well-tolerated doses.

Treatment with CPI-0209 and the chemotherapeutic agent cisplatin demonstrated combinatorial effects on cell viability in vitro and on tumor growth in vivo, according to Constellation.

After establishing the recommended Phase 2 dose (RP2D) for the monotherapy, Constellation Pharmaceuticals will pursue expansion arms in certain tumor indications and also combination therapy development, using a biomarker strategy that will cover the assessment of ARID1A.

Constellation Pharmaceuticals by using its epigenetics platform is developing the EZH2 inhibitors CPI-1205 and CPI-0209 for the treatment of metastatic castration-resistant prostate cancer and other cancers as well as the BET inhibitor CPI-0610 for the treatment of myelofibrosis.

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