HiberCell, Inc. has successfully completed the dose escalation portion of its Phase 1b clinical trial evaluating HC-7366 in combination with Merck's belzutifan (Welireg) for patients with advanced clear cell renal cell carcinoma (ccRCC). The milestone represents a significant step forward for the first-in-class investigational therapy targeting the integrated stress response pathway.
Trial Design and Patient Enrollment
The dose escalation phase enrolled 18 patients and was designed to evaluate the safety, tolerability, and pharmacokinetics of HC-7366 while identifying recommended doses for expansion. Three dose levels of HC-7366 (20 mg, 40 mg, and 60 mg) were assessed in combination with fixed-dose belzutifan at 120 mg administered orally once daily.
All three dose levels successfully cleared their respective dose-limiting toxicity (DLT) evaluations. However, based on favorable safety and pharmacokinetic/pharmacodynamic profiles, the 40 mg and 60 mg doses of HC-7366 were selected for further evaluation in combination with belzutifan.
"We're pleased to announce the successful completion of the dose escalation phase of our trial, a key milestone in establishing the safety of combining HC-7366 with belzutifan," said Dr. Steven Gillis, Chairman and Acting CEO of HiberCell. "We're encouraged by the strong pace of enrollment and we're grateful to the clinical sites, investigators, and patients participating in the study."
Expansion Phase Progress
HiberCell announced that enrollment in the 40 mg expansion cohort is now complete. Enrollment for the 60 mg cohort is ongoing and expected to complete before the end of the second quarter of 2025. Each expansion cohort is designed to enroll 15 patients. Additionally, a separate cohort evaluating HC-7366 as monotherapy at the 60 mg dose is actively enrolling patients.
Gillis noted that the company looks forward to "assessing additional safety, PK/PD, and preliminary efficacy data from the expansion cohorts, particularly as the 40 mg and 60 mg doses have been identified as the most likely to demonstrate efficacy based on preclinical models."
Novel Mechanism of Action
HC-7366 is a first-in-class, selective, potent, small molecule investigational agent being tested in humans for the first time. The drug works by activating GCN2, one of the kinases of the integrated stress response (ISR) family that responds to amino acid deprivation and serves as a key metabolic stress sensor in cells.
While cancer cells often utilize the ISR for survival, prolonged or hyperactivation of GCN2 with HC-7366 has demonstrated the ability to slow down or stop tumor growth in preclinical studies. The mechanism may also help the immune system better recognize and attack cancer cells. HC-7366 has shown potential both as a standalone treatment and in combination with standard of care treatments in early studies of solid and liquid tumors.
HiberCell recently presented research at the American Association for Cancer Research (AACR) Annual Meeting highlighting that activation of the GCN2 pathway is associated with enhanced anti-tumor activity across multiple preclinical models.
Clear Cell Renal Cell Carcinoma Context
Clear cell renal cell carcinoma represents the most common subtype of renal cell carcinoma, a form of kidney cancer that begins in cells lining small tubes within the kidneys that help filter waste from the bloodstream. According to the American Cancer Society, more than 81,000 people in the United States are diagnosed with kidney cancer each year, with ccRCC representing the most common form.
The disease typically affects only one kidney but may involve both in some cases. In early stages, ccRCC usually does not cause noticeable symptoms, but as the cancer progresses, patients may experience blood in the urine, persistent fatigue, fever, flank pain, and unexplained weight loss.
The condition occurs approximately twice as often in men as in women and most frequently arises in individuals between the ages of 50 and 70. Risk factors include tobacco use, obesity (BMI over 25), high blood pressure, chronic kidney disease requiring dialysis, and long-term exposure to certain workplace chemicals.
