HC-7366 + Belzutifan for Kidney Cancer

Recruiting in Palo Alto (17 mi)

+14 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: HiberCell, Inc.

Disqualifiers: Diabetes, Hypertension, Bipolar, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a Phase 1b, open-label, multicenter, safety, tolerability and efficacy study of HC-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. Approximately 80 patients will be enrolled in this study (up to 20 patients will be enrolled into the HC-7366 monotherapy cohort, up to 30 patients into the combination dose escalation, and up to 30 patients into the combination dose expansion). 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 (inoperable) or metastatic RCC with predominantly clear cell histology, irrespective of VHL gene mutation status.

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.

What data supports the effectiveness of the drug Belzutifan for kidney cancer?

Belzutifan has shown promising results in treating advanced clear cell renal cell carcinoma, both alone and in combination with other drugs, by inhibiting a protein that helps cancer cells grow. In studies, it demonstrated anti-tumor activity and was well tolerated, suggesting it could be an effective treatment option for this type of kidney cancer. ^{1 2 3 4 5}

How is the drug HC-7366 + Belzutifan unique for kidney cancer treatment?

The drug combination of HC-7366 and Belzutifan is unique because Belzutifan is a small molecule inhibitor that targets hypoxia-inducible factor-2α (HIF-2α), which is involved in the growth of kidney cancer cells. This approach is different from traditional treatments as it specifically targets a pathway that is often active in kidney cancer, offering a new option for patients who have progressed after other therapies. ^{1 3 4 5 6}

Research Team

Eligibility Criteria

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.

I am 18 years old or older.

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.

Trial Timeline

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

Treatment Details

Interventions

• Belzutifan (Other)
• HC-7366 (Other)

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.

Participant Groups

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

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

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. England 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

LITESPARK-011: belzutifan plus lenvatinib vs cabozantinib in advanced renal cell carcinoma after anti-PD-1/PD-L1 therapy. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Belzutifan: First Approval. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Targeting hypoxia-inducible factor pathways in sporadic and Von Hippel-Lindau syndrome-related kidney cancers. [2022]