HC-7366 + Belzutifan for Kidney Cancer

Recruiting at 15 trial locations

Overseen By Paulette Mattson

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: HiberCell, Inc.

Disqualifiers: Diabetes, Hypertension, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced kidney cancer that cannot be surgically removed or has metastasized. The goal is to determine the safest and most effective dose of two drugs, HC-7366 (an experimental treatment) and belzutifan, when used together. The trial tests HC-7366 both alone and in combination with belzutifan. Suitable participants have clear cell renal cell carcinoma that has advanced locally or spread further. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that HC-7366 has undergone early testing to assess its safety. These studies aimed to determine the optimal dose patients can tolerate. While researchers continue to study HC-7366 for its effects on kidney cancer, some earlier research explored its potential benefits.

For the combination of HC-7366 with belzutifan, studies have shown promising results. Researchers examined how these drugs interact in lab models of kidney cancer. The current trial seeks to identify the safest dose when using these two drugs together.

As this trial is in its early stages, researchers are still assessing how well patients tolerate these treatments. The goal is to ensure safety before progressing to larger studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about HC-7366 and belzutifan for kidney cancer because they target the disease in innovative ways. Belzutifan works by inhibiting HIF-2α, a protein that promotes tumor growth under low-oxygen conditions, which is a different approach compared to traditional treatments like tyrosine kinase inhibitors or mTOR inhibitors. Meanwhile, HC-7366 is being explored for its potential to enhance the immune response against cancer cells. This combination could offer a powerful new option for patients, potentially improving outcomes by tackling the cancer on multiple fronts.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

Research has shown that HC-7366 may help treat clear cell renal cell carcinoma (ccRCC), a type of kidney cancer. In lab studies, HC-7366 triggered a stress response that slowed cancer cell growth. Participants in this trial may receive HC-7366 as a monotherapy, while another group will receive a combination of HC-7366 with belzutifan. In models that rely on HIF-2, a protein aiding cancer cell survival, HC-7366 showed potential benefits when used with belzutifan. This combination is believed to stop cancer cells from growing and surviving. Early data from animal studies suggest this approach could benefit patients with advanced kidney cancer. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced kidney cancer that can't be removed by surgery or has spread, and who have tried other treatments (up to five lines) without success. They should be relatively healthy otherwise, able to perform daily activities with ease, and expected to live at least three more months.

Inclusion Criteria

My organs are functioning well.

I've had 2-5 treatments for stage IV cancer, including specific drug types.

Has a life expectancy of 3 months or greater as determined by the treating physician

Exclusion Criteria

I haven't had cancer treatment with antibodies in the last 4 weeks.

I had major surgery less than 3 weeks ago.

I have another cancer that has worsened or needed treatment in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

HC-7366 Monotherapy

Participants receive HC-7366 monotherapy to determine the maximum tolerated dose

Duration not specified

Combination Dose Escalation

Participants receive HC-7366 in combination with belzutifan to determine the maximum tolerated dose

Duration not specified

Combination Dose Expansion

Participants receive the determined dose of HC-7366 in combination with belzutifan to further evaluate safety and efficacy

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belzutifan
• HC-7366

Trial Overview The study tests HC-7366 alone and combined with Belzutifan in patients. It's designed in parts: first testing HC-7366 solo, then finding the safest high dose when used together, followed by a larger group trying this combo. The goal is to see how well these drugs work against kidney cancer.

How Is the Trial Designed?

Group I: Monotherapy Experimental Treatment 1 Intervention

Participants will receive HC-7366 monotherapy \[dose to be determined\] daily

Group II: Combination Experimental Treatment 2 Interventions

Participants will receive HC-7366 monotherapy \[dose to be determined\] in combination with belzutifan \[120 mg\] daily

Belzutifan is already approved in United States for the following indications:

Approved in United States as Welireg for:

• Advanced renal cell carcinoma (RCC) following a PD-1 or PD-L1 inhibitor and a VEGF TKI
• Von Hippel-Lindau disease-associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors

Who Is Running the Clinical Trial?

HiberCell, Inc.

Lead Sponsor

Trials

20

Recruited

860+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Belzutifan (MK-6482), a small-molecule HIF-2 alpha inhibitor, shows significant efficacy in treating renal cell carcinomas (RCC) associated with Von Hippel-Lindau (VHL) syndrome and in sporadic RCC that has progressed after immune checkpoint inhibitors (ICIs).

This review highlights the potential of HIF inhibitors as a new treatment option for advanced RCC patients, particularly those who have limited options after ICI therapy, aiming to delay surgery and preserve kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting hypoxia-inducible factor pathways in sporadic and Von Hippel-Lindau syndrome-related kidney cancers. Iacovelli, R., Arduini, D., Ciccarese, C., et al.[2022]

Belzutifan (Welireg™) is an oral medication that inhibits HIF-2α and has been approved in the USA for treating patients with von Hippel-Lindau (VHL) disease who have associated renal cell carcinoma (RCC) and other tumors, marking a significant advancement in targeted cancer therapy.

Clinical studies are ongoing to evaluate the efficacy of belzutifan in treating other solid tumors, including clear cell renal cell carcinoma (ccRCC) and pancreatic neuroendocrine tumors (pNET), indicating its potential for broader applications in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belzutifan: First Approval. Deeks, ED.[2022]

In a phase 2 study involving 52 patients with advanced clear cell renal cell carcinoma who had previously received immunotherapy, the combination of belzutifan and cabozantinib showed promising antitumour activity, with 30.8% of patients achieving a confirmed objective response, including one complete response.

The treatment was associated with manageable safety concerns, primarily hypertension (27% of patients), and serious treatment-related adverse events occurred in 29% of patients, indicating that while the combination therapy is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study. Choueiri, TK., McDermott, DF., Merchan, J., et al.[2023]

Belzutifan, a first-in-class HIF-2α inhibitor, shows promising antitumor activity in patients with clear cell renal cell carcinoma (RCC) who have previously been treated, indicating its potential as a new treatment option.

The ongoing phase III study is comparing the combination of belzutifan with lenvatinib against cabozantinib in patients with advanced RCC who have progressed after anti-PD-1/PD-L1 therapy, addressing a significant need for effective treatments in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy. Motzer, RJ., Schmidinger, M., Eto, M., et al.[2023]

The HIF-2α inhibitor, belzutifan, has shown effectiveness in treating advanced clear-cell renal cell carcinoma in the LITESPARK-005 and -003 trials, both as a standalone treatment and in combination with VEGFR tyrosine kinase inhibitors.

These promising results suggest that belzutifan could be used more broadly in cancer treatment, potentially extending its application beyond just von Hippel-Lindau disease-associated cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding "Practice-Changing" Belzutifan's Reach in RCC. [2023]

In a phase 1 study involving 98 patients with advanced solid tumors and clear cell renal cell carcinoma (ccRCC), belzutifan (MK-6482) was found to be well tolerated, with no dose-limiting toxicities at doses up to 160 mg, establishing a recommended phase 2 dose of 120 mg once daily.

Belzutifan demonstrated preliminary anti-tumor activity in ccRCC, with a 25% objective response rate and a median progression-free survival of 14.5 months, indicating its potential as an effective treatment option for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Choueiri, TK., Bauer, TM., Papadopoulos, KP., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS609

A phase 1b, open-label, safety, tolerability, and efficacy ... These preclinical effects of HC-7366 suggest potential therapeutic benefit in clear cell renal cell carcinoma (ccRCC) and rationale for ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06234605

NCT06234605 | A Study of HC-7366 in Combination With ... The primary purpose of this study is to determine the maximum tolerated dose of HC-7366 in combination with belzutifan in patients with locally advanced ( ...

3. kcrs.kidneycan.org kcrs.kidneycan.org/wp-content/uploads/2024/07/5_Rana_McKay.pdf

A Phase 1b, Open-Label, Safety, Tolerability, and Efficacy ... GCN2 activation by HC-7366 drives the Integrated Stress. Response (ISR), resulting in translation inhibition and delayed cell cycle progression in cancer cells.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11301875/

5 A Phase 1b, Open-Label, Safety, Tolerability, and ... HC-7366 (0.5-1 mg/kg), combined with belzutifan (1 mg/kg), exhibited combination benefit in HIF-2 dependent A-498 and 786-O RCC xenografts, ...

5. yalemedicine.org yalemedicine.org/clinical-trials/hc366-rcc2311-mk-6482-030

7366 in Combination With Belzutifan (WELIREG™ ... This is a multipart study that consists of a HC-7366 monotherapy cohort, a combination dose escalation, and a combination dose expansion.

6. curetoday.com curetoday.com/view/dose-escalation-complete-in-kidney-cancer-trial-of-hc-7366-plus-welireg

Dose Escalation Complete in Kidney Cancer Trial of HC ... A phase 1b study evaluating treatment with HC-7366 in combination with Welireg (belzutifan) for patients with advanced clear cell renal cell ...