Benzinga | Dec 21, 2020 06:31AM EST

ORIC Pharmaceuticals Announces Initiation of Expansion Cohorts in Phase 1b Study of ORIC-101

Initiated Part II expansion of the Phase 1b study of ORIC-101 in combination with Abraxane (nab-paclitaxel) using recommended Phase 2 dose selected from Part I of the study

Expansion cohorts will enroll patients with pancreatic ductal adenocarcinoma, ovarian cancer, triple negative breast cancer and other advanced solid tumors

SOUTH SAN FRANCISCO, Calif. and SAN DIEGO, Dec. 21, 2020 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (NASDAQ:ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today announced the initiation of the Part II dose expansion portion of the Phase 1b study of ORIC-101, a potent and selective glucocorticoid receptor (GR) antagonist, in combination with Abraxane (nab-paclitaxel) for the treatment of advanced solid tumors.

"We are pleased to announce continued progress of our GR program with the selection of the recommended Phase 2 dose of ORIC-101 in combination with Abraxane triggering the initiation of multiple expansion cohorts in cancers with high unmet medical need," said Jacob Chacko, M.D., president and chief executive officer of ORIC. "I am grateful to the patients and their families, investigators, and our employees who have helped us reach this important milestone."

The Phase 1b clinical study of ORIC-101 in combination with nab-paclitaxel is a non-randomized, multicenter, open-label study conducted in two parts, intended to establish the recommended Phase 2 dose (RP2D), safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity when administered to patients with advanced or metastatic solid tumors.

In the Part I dose escalation portion of the study, five cohorts of patients across multiple solid tumors were enrolled to evaluate ORIC-101 doses ranging from 80 to 240 mg administered orally in both intermittent and continuous once daily dosing regimens, in combination with either 75 or 100 mg/m2 nab-paclitaxel. Following the completion of the dose escalation portion of the study, the RP2D was determined to be 160 mg of ORIC-101 continuous once daily dosing and 75 mg/m2 of nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle, without requirement for prophylactic granulocyte-colony stimulating factor. The selection of RP2D was based upon the totality of safety, pharmacokinetic and pharmacodynamic data demonstrating a well-tolerated regimen that achieved ORIC-101 exposures leading to demonstrable target engagement and GR inhibition.

For the Part II dose expansion portion of the study, up to 132 patients are expected to be enrolled across four cohorts, including pancreatic ductal adenocarcinoma, ovarian cancer, triple negative breast cancer, and other advanced solid tumors. Patients in the dose expansion portion of the study will be required to have previously progressed on a taxane-containing regimen, with retrospective analysis of GR expression and other potentially predictive biomarkers.

The company also announced dose escalation remains ongoing with ORIC-101 in combination with Xtandi (enzalutamide) with no dose-limiting toxicities observed to date. The Phase 1b clinical study of ORIC-101 in combination with enzalutamide is a non-randomized, multicenter, open-label study to establish the RP2D, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity when administered to patients with metastatic prostate cancer. Dose exploration has been conducted in three cohorts to date, with 240 mg of ORIC-101 and 160 mg of enzalutamide both administered continuously once daily currently ongoing.