FDA Fast Tracks IDE161 for BRCA1/2-Mutated HR+/HER2- Breast Cancer

• Under the fast track designation (FTD), the IDE161 development program is eligible for expedited regulatory review processes including potential eligibility for a new drug application (NDA), accelerated approval, and priority review of an NDA.

• This marks the second indication in the IDE161 development program to receive FTD, following the designation for patients with BRCA1/2-mutated ovarian cancer.

• These clinical program updates for IDE161 are targeted for Q4 2023

3d rendered illustration - breast cancer © SciePro - stock.adobe.com

The FDA has granted a FTD to IDE161 for the treatment of adult patients with advanced or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer with germline or somatic BRCA 1/2 mutations who have progressed following treatment with at least 1 prior line of a hormonal therapy, a CDK4/6 inhibitor therapy and a poly (ADP-ribose) PARP inhibitor therapy.¹

"The [United States]. 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," said Darrin Beaupre, MD, chief medical officer at IDEAYA Biosciences, in a 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."

IDE161 is a potent, selective, small-molecule inhibitor of PARG. The agent has a mechanistically-differentiated target in the clinically-validated DNA damage repair pathway.

The fast track designation allows the IDE161 development program in BRCA1/2-mutated breast cancer to be eligible for a variety of expedited regulatory review processes. Some of these include more frequent FDA interactions with the FDA, the potential eligibility for rolling review of an NDA, potential accelerated approval, and priority review of an NDA.

This is the second FTD for IDE161, following the recent regulatory decision for IDE161 as treatment for adult patients with BRCA1/2-mutated, advanced, or metastatic ovarian cancer who are platinum resistant and have received prior antiangiogenic and therapy with a PARP inhibitor. These data were based on the FDA's review of preclinical and emerging clinical efficacy and tolerability data from a first-in-human phase 1 study (NCT05787587).²

In the first-in-human, phase 1 study, the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of IDE161 are being evaluated, along with the preliminary efficacy of the agent in patients with solid tumors with homologous recombination deficiency (HRD).³

According to early clinical data from the dose-escalation cohorts of the study, there was preliminary tumor shrinkage in some patients who had solid tumors with HRD. Patients included those with BRCA 1/2-mutated endometrial cancer and colon cancer.^1,2

With these promising data, expansion into priority tumor indications are supported, and the study will continue evaluating the optimal move-forward dose for the phase 2 expansion portion of the trial. Here, patients with HRD-associated breast cancer and ovarian cancer will be evaluated. The study will also include a basket of other selected solid tumors. For patients with breast cancer, the focus is on estrogen receptor-positive, HER2-negative, HRD-positive tumors.

IDEAYA is targeting program updates for IDE161 in the fourth quarter of 2023.

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, Inc. September 27, 2023. Accessed September 28, 2023. https://tinyurl.com/mpv6mpdx

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, Inc. September 26, 2023. Accessed September 28, 2023. https://tinyurl.com/fmnns4dd

3. A study of PARG inhibitor IDE161 in participants with advanced solid tumors. ClinicalTrials.gov. Updated March 28, 2023. Accessed September 28, 2023. https://tinyurl.com/5n88hswb