On June 2, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported initial data from an ongoing Phase 1b study evaluating ORIC-101, a glucocorticoid receptor antagonist, in combination with nab-paclitaxel, in advanced solid tumors. The data will also be presented in two posters at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting to be held June 4 – 8, 2021 (Press release, ORIC Pharmaceuticals, JUN 2, 2021, View Source [SID1234583387]).
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"We are excited to share initial data from our ORIC-101 clinical program in patients with advanced solid tumors. We are pleased that the combination was well tolerated without evidence of drug-drug interaction and has demonstrated both tumor regression and prolonged stable disease in multiple heavily pretreated tumors," said Pratik S. Multani, MD, chief medical officer. "Although early, we are particularly intrigued by the potential benefit seen in patients with late-line relapsed pancreatic cancer previously treated with nab-paclitaxel, as any retreatment benefit in such patients would not be expected. We are continuing to enroll patients in the expansion cohorts and look forward to reporting updated data from the Phase 1b trial in 2022."
"Having been involved with this study from its design stage, I feel we have developed an optimal combination for this heavily pretreated patient population," said Professor Pamela Munster, MD, Director of the University of California San Francisco’s Early Phase Clinical Trials Unit, and trial investigator and senior author of the ASCO (Free ASCO Whitepaper) poster. "I’m impressed by the extended time on treatment we’ve seen in patients with late-line pancreatic cancer; seeing clinical activity in these patients is quite remarkable."
Trial Design and Initial Results from Phase 1b Clinical Trial
The Phase 1b clinical trial of ORIC-101 in combination with nab-paclitaxel is a single arm, 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 (G-CSF).
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 (PDAC), ovarian cancer, triple negative breast cancer, and other advanced solid tumors. Enrollment continues in the Part II dose expansion cohorts at 12 clinical sites across the United States. Patients in the dose expansion portion of the study are required to have previously progressed on a taxane-based therapy, with retrospective analysis of GR expression and other potentially predictive biomarkers.
Safety Analyses:
As of March 31, 2021, a total of 31 patients were enrolled across Parts I/II of the study, which included 12 patients treated at non-RP2D doses and 19 patients treated at the RP2D of 160 mg of ORIC-101 continuous once daily dosing and 75 mg/m2 of nab-paclitaxel.
Patients treated at the RP2D were heavily pretreated, with a median of four prior therapies, and all had previously received a taxane-based therapy.
As of the database cutoff date of April 21, 2021, the RP2D was well tolerated; treatment-related adverse events were primarily Grade 1 or 2, with only three Grade 3 events, which all resolved with dose interruption.
There were no treatment-related discontinuations and no requirement for prophylactic G-CSF at the RP2D.
Preliminary Antitumor Activity (as of the database cutoff date of April 21, 2021):
The efficacy evaluable population included a total of 23 patients who had an opportunity for at least one on-treatment tumor assessment.
Five partial responses were observed, one confirmed and four unconfirmed, including in heavily pretreated patients with PDAC, endometrial and breast cancers, who previously progressed on or after a taxane-based therapy.
Further evidence of antitumor activity was demonstrated by prolonged disease stabilization across multiple solid tumors, including PDAC, breast, gastric, esophageal, and testicular cancers.
Notably, three of the four efficacy evaluable patients with late-line relapsed PDAC treated at the RP2D demonstrated extended progression free survival ranging from 3.6 months to 5.3+ months in the third-line or later setting, despite having already previously progressed on nab-paclitaxel.
The poster presentations will be on the ORIC website on June 4, 2021.
ORIC-101 is also being evaluated in a Phase 1b trial in combination with Xtandi (enzalutamide) in metastatic prostate cancer, which is also currently enrolling to the dose expansion portion of the study, and initial interim safety, efficacy, and translational data are expected in the second half of 2021.
Webcast and Conference Call
ORIC will host a conference call and webcast, today at 5:00 p.m. ET. To participate in the conference call, please dial (833) 651-0991 (domestic) or (918) 922-6080 (international) and refer to conference ID 4783288. A live webcast and audio archive of the conference call will be available through the investor section of the company’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.
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) Abraxane (nab-paclitaxel) in advanced or metastatic solid tumors and (2) Xtandi (enzalutamide) in metastatic prostate cancer.