FDA Fast Tracks HC-7366 for Relapsed/Refractory AML

The FDA granted a fast track designation to HC-7366 for relapsed/refractory acute myeloid leukemia.

The FDA has granted fast track designation to HC-7366, a novel GCN2 kinase modulator, for the treatment of adults with relapsed/refractory acute myeloid leukemia (AML).¹

HC-7366 is a first-in-class, selective, potent small-molecule activator of GCN2 kinase, a key component of the integrated stress response family that responds to amino acid deprivation and acts as a critical metabolic stress sensor in cells. Preclinical models have shown that prolonged or hyperactivation of GCN2 through HC-7366 both alone and in combination with standard-of-care agents generated antitumor and immunomodulatory activity across solid tumors and hematologic malignancies. This approach capitalizes on the dependency of cancer cells on ISR, potentially disrupting their adaptive survival mechanisms.

The agent is currently under development across solid and liquid tumors. Ongoing studies include a phase 1b trial (NCT06285890) of HC-7366 in combination with venetoclax (Venclexta) and azacitidine (Vidaza) for patients with relapsed/refractory AML or myelodysplastic syndrome (MDS) AML; and a phase 1b/2 study (NCT06234605) of HC-7366 in combination with belzutifan (Welireg) for patients with clear cell renal cell carcinoma.

“We are proud to announce the grant of fast track designation by the FDA,” Jonathan Lanfear, president and chief executive officer of HiberCell, stated in a news 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.”

Overview of the Phase 1b Study in AML

The single-arm study will evaluate the safety, tolerability, and preliminary efficacy of HC-7366 in combination with azacitidine and venetoclax 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

In the dose-escalation phase, patients must also have relapsed/refractory disease other than acute promyelocytic leukemia, no available standard treatment options, and an ECOG performance status between 0 to 2.

The study plans to enroll approximately 18 patients onto the study. Patients will receive single-agent HC-3766 on days 1 to 28 during cycle 1. For cycles 2 and beyond, HC-3766 will be taken 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.

Assessment of safety and adverse effects (AEs) serves as the study’s primary end point. The study’s primary objective is to find a recommended dose of HC-7366 that can be given in combination with azacitidine and venetoclax. Key secondary objectives include 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.

The study was initiated on May 20, 2024, and is being conducted at The University of Texas MD Anderson Cancer Center in Houston. It has an estimated completion date of December 31, 2029.² Additional combination and monotherapy expansion cohorts may be included based on observations in the dose escalation portion.¹

“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 concluded. “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.”

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 24, 2024. Accessed October 25, 2024. https://www.globenewswire.com/news-release/2024/10/23/2967964/0/en/HiberCell-Receives-FDA-Fast-Track-Designation-for-HC-7366-for-the-Treatment-of-Relapsed-or-Refractory-Acute-Myeloid-Leukemia-AML.html

2. Phase I study of HC-7366 with azacitidine and venetoclax for acute myeloid leukemia.ClinicalTrials.gov. Updated August 9, 2024. Accessed October 25, 2024. https://clinicaltrials.gov/study/NCT06285890