A Study of HC-7366 in Combination With Belzutifan (WELIREG™) in Patients With Renal Cell Carcinoma

Renal Cell Carcinoma Clinical Trial

Official title:

A Phase 1b, Open-Label, Safety, Tolerability, and Efficacy Study of HC- 7366 in Combination With Belzutifan (WELIREG™) in Patients With Locally Advanced (Inoperable) or Metastatic Renal Cell Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06234605
• Other study ID #: HC366-RCC2311
• Secondary ID: MK-6482-030
• Status: Recruiting
• Phase: Phase 1
• Start date: April 29, 2024
• Est. completion date: November 2027

Study information

• Verified date: April 2024
• Source: HiberCell, Inc.
• Contact: HiberCell
• Phone: 651-675-0300
• Email: HC366-RCC2311_StudyMailbox[@]catalystcr.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: November 2027
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has diagnosis of locally advanced (inoperable) or metastatic RCC with a predominant clear cell component
• Be age 18 years or older (male or female) at the time of consent
• Patients with progressive disease after receipt of at least 2 and no more than 5 prior lines of therapy for metastatic (stage IV) disease, including but not limited to VEGF-directed tyrosine kinase inhibitors (TKIs), high-dose IL-2, immune checkpoint inhibitors, or Mtor inhibitors alone or in combination.
• Has adequate organ function
• Has ECOG performance score of 0-1
• Has at least one measurable lesion as per RECIST 1.1.
• Has a life expectancy of 3 months or greater as determined by the treating physician.

Exclusion Criteria:

• Has received prior treatment with belzutifan or another HIF-2a inhibitor
• Has received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) =2 weeks before allocation.
• Has received any type of systemic anticancer antibody (including investigational antibody) =4 weeks before allocation.
• Has participated in a study of an investigational agent and received study therapy within 4 weeks of the first dose of treatment
• Has had history of major surgery < 3 weeks before allocation
• Has received prior radiotherapy within 2 weeks before allocation
• Have clinically significant cardiovascular disease within 6 months from first dose of study drug administration
• Has known additional malignancy that is progressing or required active treatment within the past 5 years
• Has a history of or known active central nervous system metastases and/or carcinomatous meningitis
• Is unable to swallow orally administered medication intact or has a history or current evidence of a gastrointestinal disorder
• Has known human immunodeficiency virus (HIV) and/or hepatitis B or C infections
• Has a history of or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, or interfere with the individual's ability to cooperate with the requirements of the study
• Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through 90 days after the final administration of the study drug.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• HC-7366
HC-7366 is a novel, orally administered, highly selective and potent general control nonderepressible 2 (GCN2) kinase activator.
• Belzutifan
Belzutifan is a potent and selective HIF-2a inhibitor

Locations

Country	Name	City	State
United States	University of California San Diego Moores Cancer Center	La Jolla	California
United States	Rocky Mountain Cancer Centers, LLP	Lone Tree	Colorado
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	HealthPartners Cancer Research Center	Saint Paul	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
HiberCell, Inc.	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of MTD and RP2D (combination cohorts only)	To identify the maximum tolerated dose (MTD) and/ or recommended Phase 2 dose (RP2D), and evaluate the safety, tolerability and dose-limiting toxicities (DLTs) 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	Approximately 30 months
Primary	Occurrence of dose limits toxicities in the dose-escalation period		Approximately 30 months
Primary	Number of participants who experience treatment-emergent adverse events (TEAEs) and treatment-related TEAEs and the severity of these events		Approximately 30 months
Primary	Number of participants who experience TEAEs leading to premature discontinuation		Approximately 30 months
Primary	Number of participants who experience laboratory abnormalities		Approximately 30 months
Primary	Number of participants who experience abnormalities observed in 12-lead ECG parameters.		Approximately 30 months
Primary	Number of participants who experience abnormalities observed in vital signs measurements.	Number of participants who experience abnormalities observed in vital signs measurements.	Approximately 30 months
Secondary	Overall response rate (ORR): percentage of participants who achieved documented complete response (CR) + confirmed partial response (PR) per RECIST Version 1.1		Approximately 30 months
Secondary	Duration of response (DOR): time from first response (CR or PR) to the date of progression or death from any cause, whichever occurs first per RECIST Version 1.1		Approximately 30 months
Secondary	Time to response (TTR): time from first dose to first documented response		Approximately 30 months
Secondary	Progression-free survival (PFS) and PFS at 6 months: time from first dose to documented disease progression or death due to any cause, whichever occurs first per RECIST Version 1.1		Approximately 30 months
Secondary	Median overall survival (OS) and 1-yr OS: time from the first day of study intervention to death due to any cause		Approximately 30 months
Secondary	Area under the plasma concentration versus time curve from time 0 until the last measurable concentration (AUC 0-last [ng·hr/mL])		Approximately 30 months
Secondary	Area under the plasma concentration versus time curve from time 0 to 24 hours (AUC 0-24 [ng·hr/mL])		Approximately 30 months
Secondary	Area under the plasma concentration versus time curve from time 0 extrapolated to infinity (AUC 0-8 [ng·hr/mL])		Approximately 30 months
Secondary	Area under the plasma concentration versus time curve over a dosing interval (AUC 0-t [ng·hr/mL])		Approximately 30 months
Secondary	Maximum plasma concentration (Cmax [ng/mL])		Approximately 30 months
Secondary	Time of the maximum observed plasma concentration (tmax [hour])		Approximately 30 months
Secondary	Apparent total clearance (CL/F [L/h])		Approximately 30 months
Secondary	Apparent volume of distribution during the terminal phase (Vz/F [L])		Approximately 30 months
Secondary	Apparent terminal elimination half-life (t1/2 [h])		Approximately 30 months
Secondary	Accumulation ratio based on AUC0-t (AR AUC)		Approximately 30 months