FDA Grants Fast Track Designations for Two Breast Cancer Therapies

The FDA has granted fast track designation to ART6043 plus olaparib (Lynparza) for patients with germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer who have not received prior treatment with a PARP inhibitor. Separately, BriaCell Therapeutics' pivotal Phase 3 study of Bria-IMT plus immune checkpoint inhibitor in metastatic breast cancer is being conducted under FDA Fast Track designation, reflecting the significant unmet medical need in metastatic breast cancer.

ART6043 is a potentially first-in-class DNA polymerase θ inhibitor. The agent is an orally bioavailable and a small-molecule inhibitor. DNA polymerase θ is an enzyme that is observed in cancer cells but mostly omitted in healthy cells. When adding olaparib to molecularly defined solid tumors, including those with BRCA mutation and PARP inhibitor resistance, the target engagement will be enhanced, and anti-tumor activity will be incurred while maintaining tolerability.

ART6043 plus olaparib was assessed in a phase 1/2a trial (NCT05898399) for patients with solid tumors who have DNA damage response pathways, including those with germline BRCA mutations in HER2-negative breast cancer. Results showed ART6043 demonstrating a benign tolerability profile as a monotherapy, and no additional toxicity when it was combined with olaparib. The oral once-daily dosing was supported by pharmacokinetic data as convenient, and there was no drug-drug interaction between ART6043 and olaparib. ART6043 pharmacodynamic data were enhanced with olaparib for those who had tumor regression.

BriaCell Therapeutics has received a fifth consecutive positive recommendation from an independent Data Safety Monitoring Board for its pivotal Phase 3 Bria-ABC study evaluating Bria-IMT in combination with an immune checkpoint inhibitor in metastatic breast cancer (NCT06072612). Following its review, the DSMB raised no safety concerns and recommended that the study continue without modifications. DSMB meetings occur quarterly in accordance with the study protocol.

In the phase 1/2a trial of ART6043, part A assessed the number of patients with dose-limiting toxicities as the primary end point; in part B1, it was the number of patients with adverse effects; and in part B2, it was progression-free survival. Secondary end points included best overall response, objective response rate, disease control rate, duration of response, and change in tumor size.

Patients were eligible for treatment if they had discontinued all previous chemotherapeutic agents, non-hormonal targeted therapy, or investigational drugs at least 21 days or 5 half-lives, whichever is shorter; had resolution of all toxicities of prior therapy or surgical procedures; a performance status of 0 to 2; and adequate organ function.