FDA Fast Tracks HC-7366 in Relapsed/Refractory Acute Myeloid Leukemia

• The FDA has granted fast track designation to HC-7366 for the treatment of adult patients with relapsed/refractory acute myeloid leukemia (AML).
• HC-7366 is a novel, first-in-class, selective, potent small-molecule, GCN2 kinase modulator.
• Multiple studies are investigating HC-7366 for the treatment of solid and liquid tumors, including a single-arm study (NCT06285890) of HC-7366 with azacitidine and venetoclax (Venclexta) in AML or myelodysplastic syndrome (MDS) AML.

HC-7366 has received fast track designation from the FDA for the treatment of adult patients with relapsed/refractory AML.¹

“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.”

The agent, a first-in-class, selective, potent small-molecule activator of GCN2 kinase, is currently being investigated for the treatment of various solid and liquid tumors. In a phase 1b trial (NCT06285890), HC-7366 is being evaluated when given in combination with venetoclax and azacitidine for the treatment of relapsed/refractory AML or MDS AML. A phase 1b/2 study (NCT06234605) is also evaluating the combination of HC-7366 with belzutifan (Welireg) in clear cell renal cell carcinoma.

Preclinically, prolonged or hyperactivation of GCN2 through HC-7366 was observed when the agent was given alone and in combination with standard-of-care agents, leading to antitumor and immunomodulatory activity across solid tumors and hematologic malignancies.

Acute myeloid leukemia (AML) cells in blood flow: © LASZLO - stock.adobe.com

“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.”

In the single-arm study of HC-7366 plus azacitidine and venetoclax, experts are looking to determine the combination’s safety, tolerability, and preliminary efficacy in patients at least 18 years of age with a confirmed diagnosis of AML or MDS AML with 10% to 19% bone marrow blasts per the International Consensus Classification 2022 or the World Health Organization 2022 classification.²

The study started on May 20, 2024, and is currently being conducted at The University of Texas MD Anderson Cancer Center in Houston, Texas. The study is expected to enroll approximately 18 patients onto the trial.

All patients are required to have adequate hepatic function and renal function. Enrollment requirements for the dose-escalation phase states that patients must have relapsed/refractory disease (excluding acute promyelocytic leukemia), no available standard treatment options, and an ECOG performance status of 0, 1, or 2.

Once enrolled, patients will be given single-agent HC-3766 on days 1 to 28 during cycle 1. HC-3766 will then be given once daily on days 1 to 28 in combination with azacitidine administered either intravenously or subcutaneously on days 1 to 7 of each cycle and oral venetoclax once daily on days 1 to 28 for cycles 2 and beyond.

The primary end point of the study is to evaluate the safety and adverse effects (AEs). The secondary end points of the study are to evaluate the estimated rates of complete response (CR)/CR with partial hematologic recovery/CR with incomplete count recovery by 4 cycles, overall response rate, rate of minimal residual disease negativity by 4 cycles, overall survival, and relapse-free survival of the combination.

The estimated completion date of the trial is December 31, 2029.

REFERENCES:

1. HiberCell receives FDA fast track designation for HC-7366 for the treatment of relapsed or refractory Acute Myeloid Leukemia (AML). News release. October 23, 2024. Accessed October 28, 2024. https://tinyurl.com/2sxha38n

2. Phase I study of HC-7366 with azacitidine and venetoclax for acute myeloid leukemia.ClinicalTrials.gov. Updated August 9, 2024. Accessed October 28, 2024. https://clinicaltrials.gov/study/NCT06285890