Dose Escalation Complete in Kidney Cancer Trial of HC-7366 Plus Welireg

A phase 1b study evaluating treatment with HC-7366 in combination with Welireg (belzutifan) for patients with advanced clear cell renal cell carcinoma (ccRCC) has successfully completed the dose escalation portion of the clinical trial, according to a news release from HiberCell, Inc.

The news release goes on to explain that HC-7366 is an activator of the integrated stress response (ISR) kinase GCN2 and Welireg is an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor.

“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 Welireg,” Dr. Steven Gillis, chairman and acting CEO of HiberCell, stated in the news release. “We’re encouraged by the strong pace of enrollment and we’re grateful to the clinical sites, investigators, and patients participating in the study. We look forward to assessing additional safety, PK/PD, and preliminary efficacy data from the expansion cohorts, particularly as the 40 milligrams (mg) and 60 mg doses have been identified as the most likely to demonstrate efficacy based on preclinical models.”

Eighteen patients were enrolled in the clinical trial, which was designed to evaluate the safety, tolerability and pharmacokinetics (the branch of pharmacology concerned with the movement of drugs within the body) of HC-7366, as well as identify the recommended doses for expansion in the dose escalation phase trial. Moreover, dose levels of 20 mg, 40 mg and 60 mg were assessed in combination with fixed-dose Welireg at 120 mg, given orally once daily. Although all three dose levels cleared the respective dose-limiting toxicity (DLT) evaluations, safety and pharmacokinetic data favored the 40 mg and 60 mg doses of HC-7366. Therefore, these doses were selected for further evaluation in combination with Welireg.

Furthermore, the news release announced that patient enrollment onto the 40 mg expansion cohort is now complete. For the 60 mg cohort, enrollment is ongoing but is expected to be completed prior to the end of the second quarter of 2025. Each expansion group is planned to include 15 patients. At the same time, a separate group is actively enrolling patients to evaluate HC-7366 as a standalone treatment at the 60 mg dose.

What is HC-7366?

HC-7366 is a first-in-class, selective, potent, small molecule investigative agent being tested in humans for the first time. It works by activating a protein called GCN2, which is one of the kinases of the integrated stress response (ISR) family. By activating the protein, it helps respond to amino acid deprivation and is a key metabolic stress sensor in cells.

Although cancer cells often use the ISR for survival, previous preclinical research has shown that prolonged or hyperactivation of GCN2 with HC-7366 can help slow down or stop tumor growth. It may also help the immune system better recognize and attack cancer. HC-7366 has shown potential on its own and when combined with standard of care treatments in early studies of both solid tumors and liquid tumors.

HC-7366 is now being tested in a phase 1b clinical trial for clear cell renal cell carcinoma, in combination with another drug called Welireg.

More Information on Advanced Clear Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), a form of kidney cancer, according to the Cleveland Clinic official website. The disease begins in the cells lining small tubes within the kidneys that help filter waste from the bloodstream. In clear cell renal cell carcinoma, these cells begin to grow and multiply rapidly, forming one or more tumors. The disease typically affects only one kidney but may, in some cases, involve both.

In the early stages, ccRCC usually does not cause noticeable symptoms. However, as the cancer progresses, individuals may begin to experience certain signs which include blood in the urine (hematuria), persistent fatigue even with adequate rest, fever, a noticeable lump near the affected kidney, pain along the side of the body (flank pain) and unexplained weight loss.

The exact cause of ccRCC is not always clear. However, several factors are known to increase the risk of developing this type of kidney cancer. These include tobacco use (such as smoking or vaping), having a body mass index (BMI) over 25, high blood pressure (hypertension) and chronic kidney disease requiring dialysis. Additional risks include long-term exposure to certain workplace chemicals like trichloroethylene, as well as prolonged use of certain over-the-counter pain medications.

Clear cell renal cell carcinoma can affect anyone, although it is more common in men than in women — occurring approximately twice as often in men. The condition most frequently arises in individuals between the ages of 50 and 70. According to the American Cancer Society, more than 81,000 people in the United States are diagnosed with kidney cancer each year, and ccRCC represents the most common form.

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