FDA Gives Fast Track Designation to IDE161 for HR+, HER2– Breast Cancer

IDE161 also recently received FDA fast track designation for patients with advanced or metastatic, germline or somatic BRCA–mutant ovarian cancer that is platinum resistant and was previously treated with a PARP inhibitor.

The FDA has granted fast track designation to selective PARG inhibitor IDE161 as a treatment for adult patients with advanced or metastatic hormone receptor–positive, HER2-negative, germline or somatic BRCA1/2-mutant breast cancer after at least 1 previous line of treatment with a hormonal therapy, a CDK4/6 inhibitor, and a PARP inhibitor, according to a press release from Ideaya Biosciences.¹

Safety, tolerability, and early efficacy for IDE161 are being assessed as part of a first-in-human phase 1 study (NCT05787587) in a population of patients with homologous recombination deficient (HRD)–positive solid malignancies. Thus far, early clinical findings have spotlighted preliminary tumor shrinkage in several patient subgroups, including those with BRCA1/2-mutant endometrial cancer and colon cancer. Investigators reported that the findings supported moving the agent into other priority tumor indications while determining the recommended phase 2 dose.

Notably, the expansion portion of the study will feature patients with HRD-positive breast cancer and ovarian cancer. In particular, the study will enroll patients with estrogen receptor–positive, HER2-negative breast cancer. Other disease types included in the study are pancreatic and prostate cancer.

“The U.S. FDA fast track designations for our potential first-in-class PARG inhibitor, IDE161, in both BRCA1/2-mutant breast and ovarian cancers reflect the potential for IDE161 to address the significant unmet medical need in these indications,” Darrin Beaupre, MD, PhD, MS, chief medical officer at IDEAYA Biosciences, said in the press release. “We are excited that IDE161 has been granted fast track status in 2 separate indications, and we look forward to providing further program updates for IDE161 in the fourth quarter of this year.”

The study has an estimated enrollment of 68 patients who will receive oral IDE-161 daily. Part 1 of the study will assess safety and tolerability, while part 2 will additionally focus on preliminary overall response rate (ORR) and duration of response (DOR). Secondary end points include pharmacokinetics.

To be included in the study, patients need to be 18 years or older with advanced or metastatic solid malignancies, evidence of genetic alterations implying HRD, and progression after at least 1 line of therapy in the advanced or metastatic setting.

Those with a primary central nervous system malignancy; impaired gastrointestinal function; active, uncontrolled infection; clinically significant cardiac abnormalities; or major surgery within 4 weeks prior to study enrollment were not eligible for the trial. Additional exclusion criteria included receiving radiotherapy within 2 weeks prior to enrolling, systemic cytotoxic chemotherapy within 4 weeks, radioimmunotherapy within 6 weeks, a therapeutic antibody within 4 weeks, or an anti-cancer small molecule within 5 half-lives or 2 weeks.

IDE161 also recently received FDA fast track designation for patients with advanced or metastatic, germline or somatic BRCA–mutant ovarian cancer that is platinum resistant and was previously treated with a PARP inhibitor.²

References

1. IDEAYA Biosciences receives fast track designation for IDE161 in a second indication for the treatment of pretreated, advanced or metastatic HR+, Her2-, BRCA1/2 mutant breast cancer. News release. Ideaya Biosciences. September 27, 2023. Accessed September 27, 2023. https://bit.ly/45aVaoj
2. IDEAYA receives fast track designation for potential first-in-class PARG inhibitor, IDE161, for treatment of pretreated, platinum-resistant advanced or metastatic ovarian cancer patients having tumors with BRCA1/2 mutations. News release. Ideaya Biosciences. September 26, 2023. Accessed September 27, 2023. https://bit.ly/3RDdoeW