On December 21, 2020 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported 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 (Press release, ORIC Pharmaceuticals, DEC 21, 2020, View Source [SID1234573143]).

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"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.

About ORIC-101

ORIC-101 is a potent and selective small molecule antagonist of the glucocorticoid receptor, which has been linked to resistance to multiple classes of cancer therapeutics across a variety of solid tumors. Preclinical in vitro and in vivo data suggest ORIC-101 is able to address key resistance mechanisms of multiple classes of cancer treatments, including taxanes and androgen receptor modulators. Based on preclinical and clinical studies, ORIC-101 is expected to have reduced drug-drug interaction liabilities than other glucocorticoid receptor antagonists. Currently, there are no glucocorticoid receptor antagonists approved by the FDA for the treatment of cancer. Following the successful completion of two Phase 1a trials in over 50 healthy volunteers, ORIC initiated two separate Phase 1b trials of ORIC-101 in combination with (1) Xtandi (enzalutamide) in metastatic prostate cancer and (2) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors.