FDA Grants Fast Track Designation to IDE161 for BRCA+, Platinum-Resistant Advanced Ovarian Cancer

September 26, 2023

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The FDA has granted fast track designation to IDE161 for the treatment of adult patients with advanced or metastatic ovarian cancer harboring germline or somatic BRCA1/2 mutations who are platinum resistant and have received prior treatment with antiangiogenic and PARP inhibitor therapies.

Darrin Beaupre, MD, PhD

The FDA has granted fast track designation to IDE161 for the treatment of adult patients with advanced or metastatic ovarian cancer harboring germline or somatic BRCA1/2 mutations who are platinum resistant and have received prior treatment with antiangiogenic and PARP inhibitor therapies.¹

IDE161 is a potent and selective poly (ADP-ribose) glycohydrolase (PARG) inhibitor. PARG regulates DNA repair in the same biochemical pathway as PARP, and inhibition of PARG could disrupt the DNA damage repair cycle, leading to cell death.²

“We are extremely pleased to receive the US FDA fast track designation for IDE161 based on the FDA’s review of preclinical and emerging clinical efficacy and tolerability data,” Darrin Beaupre, MD, PhD, chief medical officer at IDEAYA Biosciences, stated in a news release.¹“We recently reported preliminary clinical proof-of-concept with expansion into priority homologous recombination deﬁcient [HRD]–positive solid tumor indications in our phase 1 clinical trial [NCT05787587]. The fast track designation has been provided for platinum-resistant, BRCA1/2-mutant, advanced or metastatic ovarian cancer, which represents a serious condition, and acknowledges the potential for IDE161 to treat this indication.”

The first-in-human phase 1 trial is evaluating IDE161 in the treatment of patients with advanced HRD-positive solid tumors. Early findings from dose-escalation cohorts have demonstrated that IDE161 elicited preliminary tumor shrinkage in multiple patients with HRD-positive solid tumors, including one patient with BRCA1/2-mutated endometrial cancer. These findings supported expansion into priority tumor indications, and evaluation is ongoing to determine the optimal dose for phase 2 expansion.

To enroll, patients must be at least 18 years of age with advanced or metastatic solid tumors who have documented evidence of genetic HRD alterations.³ Disease progression on at least one prior line of standard-of-care (SOC) therapy in the advanced or metastatic setting, or documented intolerance to SOC therapy, is required.

The expansion portion of phase 1 will include patients having HRD-positive breast cancer, HRD-positive ovarian cancer, and a basket of other selected HRD-positive solid tumors, including endometrial cancer and colorectal cancer.¹ Patients with breast cancer will be required to have estrogen receptor–positive/HER2-negative disease with HRD.

Patients with primary central nervous system tumors are not allowed to enroll. Other exclusion criteria include impairment of gastrointestinal (GI) function or GI disease that could affect the absorption of IDE161; active, uncontrolled infection; and clinically significant cardiac abnormalities.³ Patients are not allowed to undergo major surgery within 4 weeks of enrollment, receive radiation within 2 weeks prior to enrollment, receive systemic cytotoxic chemotherapy within 4 weeks of enrollment, undergo radioimmunotherapy within 6 weeks of enrollment, receive a therapeutic antibody within 4 weeks of enrollment, or receive an anticancer small molecule within 5 half-lives or 2 weeks of treatment.

During dose escalation, patients are being treated with varying doses of oral IDE161 once per day.

The primary end points include dose-limiting toxicities, treatment-emergent adverse effects, and laboratory abnormalities. Overall response rate (ORR) is also a primary end point in dose expansion. ORR during dose escalation and pharmacokinetics are secondary end points.