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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: HC-7366; Drug: Belzutifan

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: HiberCell; Phone Number: 651-675-0300; Email: HC366-RCC2311_StudyMailbox@catalystcr.com

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California San Diego Moores Cancer Center
      • Contact: Rana McKay
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Recruiting
      • HealthPartners Cancer Research Center
      • Contact: Brian Rank
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Joel Picus
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Neil Shah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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-2α 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy (Cohort 1); Participants will receive HC-7366 monotherapy [dose to be determined] daily	Drug: HC-7366; HC-7366 is a novel, orally administered, highly selective and potent general control nonderepressible 2 (GCN2) kinase activator.
Experimental: Combination Escalation (Cohort 2); Participants will receive HC-7366 20 mg plus belzutifan 120 mg daily	Drug: HC-7366; HC-7366 is a novel, orally administered, highly selective and potent general control nonderepressible 2 (GCN2) kinase activator.; Drug: Belzutifan; Belzutifan is a potent and selective HIF-2α inhibitor; Other Names: MK-6482; WELIREG™
Experimental: Combination Escalation (Cohort 3); Participants will receive HC-7366 40 mg plus belzutifan 120 mg daily	Drug: HC-7366; HC-7366 is a novel, orally administered, highly selective and potent general control nonderepressible 2 (GCN2) kinase activator.; Drug: Belzutifan; Belzutifan is a potent and selective HIF-2α inhibitor; Other Names: MK-6482; WELIREG™
Experimental: Combination Escalation (Cohort 4); Participants will receive HC-7366 75 mg plus belzutifan 120 mg daily	Drug: HC-7366; HC-7366 is a novel, orally administered, highly selective and potent general control nonderepressible 2 (GCN2) kinase activator.; Drug: Belzutifan; Belzutifan is a potent and selective HIF-2α inhibitor; Other Names: MK-6482; WELIREG™
Experimental: Combination Expansion (Cohort 5); Participants will receive HC-7366 [dose selected from escalation] plus belzutifan 120 mg daily	Drug: HC-7366; HC-7366 is a novel, orally administered, highly selective and potent general control nonderepressible 2 (GCN2) kinase activator.; Drug: Belzutifan; Belzutifan is a potent and selective HIF-2α inhibitor; Other Names: MK-6482; WELIREG™
Experimental: Combination Expansion (Cohort 6); Participants will receive HC-7366 [dose selected from escalation] plus belzutifan 120 mg daily	Drug: HC-7366; HC-7366 is a novel, orally administered, highly selective and potent general control nonderepressible 2 (GCN2) kinase activator.; Drug: Belzutifan; Belzutifan is a potent and selective HIF-2α inhibitor; Other Names: MK-6482; WELIREG™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Occurrence of dose limits toxicities in the dose-escalation period		Approximately 30 months
Number of participants who experience treatment-emergent adverse events (TEAEs) and treatment-related TEAEs and the severity of these events		Approximately 30 months
Number of participants who experience TEAEs leading to premature discontinuation		Approximately 30 months
Number of participants who experience laboratory abnormalities		Approximately 30 months
Number of participants who experience abnormalities observed in 12-lead ECG parameters.		Approximately 30 months
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 Outcome Measures

Outcome Measure	Time Frame
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
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
Time to response (TTR): time from first dose to first documented response	Approximately 30 months
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
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
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
Area under the plasma concentration versus time curve from time 0 to 24 hours (AUC 0-24 [ng∙hr/mL])	Approximately 30 months
Area under the plasma concentration versus time curve from time 0 extrapolated to infinity (AUC 0-∞ [ng∙hr/mL])	Approximately 30 months
Area under the plasma concentration versus time curve over a dosing interval (AUC 0-τ [ng∙hr/mL])	Approximately 30 months
Maximum plasma concentration (Cmax [ng/mL])	Approximately 30 months
Time of the maximum observed plasma concentration (tmax [hour])	Approximately 30 months
Apparent total clearance (CL/F [L/h])	Approximately 30 months
Apparent volume of distribution during the terminal phase (Vz/F [L])	Approximately 30 months
Apparent terminal elimination half-life (t1/2 [h])	Approximately 30 months
Accumulation ratio based on AUC0-τ (AR AUC)	Approximately 30 months

Collaborators and Investigators

• Sponsor: HiberCell, Inc.
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: kidney cancer; metastatic; ccRCC; locally advanced; HC-7366; belzutifan; WELIREG™
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Antineoplastic Agents; Belzutifan
• Other Study ID Numbers: HC366-RCC2311; MK-6482-030 (Other Identifier: Merck Sharp & Dohme LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No