The FDA has granted Fast Track designation to HC-7366 for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML). This designation is intended to facilitate the development and expedite the review of new drugs that treat serious conditions and fill an unmet medical need.
HC-7366, developed by HiberCell, is a novel, first-in-class, selective, and potent small-molecule activator of GCN2 kinase. The agent is currently being investigated for the treatment of various solid and liquid tumors. Preclinical data suggest that prolonged or hyperactivation of GCN2 through HC-7366, both alone and in combination with standard-of-care agents, leads to antitumor and immunomodulatory activity across solid tumors and hematologic malignancies.
"We are proud to announce the grant of fast track designation by the FDA," said Jonathan Lanfear, president and chief executive officer of HiberCell, in a press release. "Receiving fast track designation highlights the FDA’s recognition of the robust preclinical data generated to date for HC-7366 and the potential for HC-7366 to address the significant unmet need that exists in relapsed/refractory AML."
Ongoing Clinical Trials
A phase 1b trial (NCT06285890) is currently evaluating HC-7366 in combination with venetoclax and azacitidine for the treatment of relapsed/refractory AML or MDS AML. This single-arm study, which began in May 2024 at The University of Texas MD Anderson Cancer Center, aims to enroll approximately 18 patients. The primary endpoint is to evaluate the safety and adverse effects (AEs) of the combination. Secondary endpoints include the evaluation of complete response (CR) rates, overall response rate, minimal residual disease negativity, overall survival, and relapse-free survival.
Another phase 1b/2 study (NCT06234605) is also evaluating the combination of HC-7366 with belzutifan in clear cell renal cell carcinoma.
Trial Design and Patient Eligibility
The phase 1b trial (NCT06285890) includes patients at least 18 years of age with a confirmed diagnosis of AML or MDS AML with 10% to 19% bone marrow blasts. Patients must have adequate hepatic and renal function, relapsed/refractory disease (excluding acute promyelocytic leukemia), no available standard treatment options, and an ECOG performance status of 0, 1, or 2.
During cycle 1, patients receive single-agent HC-7366 on days 1 to 28. In subsequent cycles, HC-7366 is administered once daily on days 1 to 28 in combination with azacitidine (days 1 to 7) and oral venetoclax (days 1 to 28). The estimated completion date of the trial is December 31, 2029.
Significance of Fast Track Designation
"HC-7366 was the first GCN2-activator to enter the clinic in AML and is the only GCN2-targeting agent to receive fast track designation for the treatment of AML, validating our preclinical and translational efforts," Lanfear added. "We plan to leverage the fast track designation to work closely with the FDA to facilitate and potentially accelerate the development of HC-7366 in AML."
