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

• ClinicalTrials.gov Identifier: NCT06234605
• Recruitment Status: Recruiting
• First Posted: January 31, 2024
• Last Update Posted: May 1, 2024
• Sponsor: HiberCell, Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): HiberCell, Inc.

Tracking Information

• First Submitted Date: January 9, 2024
• First Posted Date: January 31, 2024
• Last Update Posted Date: May 1, 2024
• Actual Study Start Date: April 29, 2024
• Estimated Primary Completion Date: November 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 29, 2024)

• Determination of MTD and RP2D (combination cohorts only) [ Time Frame: Approximately 30 months ]
  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
• Occurrence of dose limits toxicities in the dose-escalation period [ Time Frame: Approximately 30 months ]
• Number of participants who experience treatment-emergent adverse events (TEAEs) and treatment-related TEAEs and the severity of these events [ Time Frame: Approximately 30 months ]
• Number of participants who experience TEAEs leading to premature discontinuation [ Time Frame: Approximately 30 months ]
• Number of participants who experience laboratory abnormalities [ Time Frame: Approximately 30 months ]
• Number of participants who experience abnormalities observed in 12-lead ECG parameters. [ Time Frame: Approximately 30 months ]
• Number of participants who experience abnormalities observed in vital signs measurements. [ Time Frame: Approximately 30 months ]
  Number of participants who experience abnormalities observed in vital signs measurements.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 29, 2024)

• Overall response rate (ORR): percentage of participants who achieved documented complete response (CR) + confirmed partial response (PR) per RECIST Version 1.1 [ Time Frame: 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 [ Time Frame: Approximately 30 months ]
• Time to response (TTR): time from first dose to first documented response [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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]) [ Time Frame: Approximately 30 months ]
• Area under the plasma concentration versus time curve from time 0 to 24 hours (AUC 0-24 [ng∙hr/mL]) [ Time Frame: Approximately 30 months ]
• Area under the plasma concentration versus time curve from time 0 extrapolated to infinity (AUC 0-∞ [ng∙hr/mL]) [ Time Frame: Approximately 30 months ]
• Area under the plasma concentration versus time curve over a dosing interval (AUC 0-τ [ng∙hr/mL]) [ Time Frame: Approximately 30 months ]
• Maximum plasma concentration (Cmax [ng/mL]) [ Time Frame: Approximately 30 months ]
• Time of the maximum observed plasma concentration (tmax [hour]) [ Time Frame: Approximately 30 months ]
• Apparent total clearance (CL/F [L/h]) [ Time Frame: Approximately 30 months ]
• Apparent volume of distribution during the terminal phase (Vz/F [L]) [ Time Frame: Approximately 30 months ]
• Apparent terminal elimination half-life (t1/2 [h]) [ Time Frame: Approximately 30 months ]
• Accumulation ratio based on AUC0-τ (AR AUC) [ Time Frame: Approximately 30 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of HC-7366 in Combination With Belzutifan (WELIREG™) in Patients With Renal Cell Carcinoma
• 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
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.
• Drug: Belzutifan
  Belzutifan is a potent and selective HIF-2α inhibitor
  Other Names:

  • WELIREG™
  • MK-6482

Study Arms

• Experimental: Monotherapy (Cohort 1)
  Participants will receive HC-7366 monotherapy [dose to be determined] daily
  Intervention: Drug: HC-7366
• Experimental: Combination Escalation (Cohort 2)
  Participants will receive HC-7366 20 mg plus belzutifan 120 mg daily
  Interventions:

  • Drug: HC-7366
  • Drug: Belzutifan
• Experimental: Combination Escalation (Cohort 3)
  Participants will receive HC-7366 40 mg plus belzutifan 120 mg daily
  Interventions:

  • Drug: HC-7366
  • Drug: Belzutifan
• Experimental: Combination Escalation (Cohort 4)
  Participants will receive HC-7366 75 mg plus belzutifan 120 mg daily
  Interventions:

  • Drug: HC-7366
  • Drug: Belzutifan
• Experimental: Combination Expansion (Cohort 5)
  Participants will receive HC-7366 [dose selected from escalation] plus belzutifan 120 mg daily
  Interventions:

  • Drug: HC-7366
  • Drug: Belzutifan
• Experimental: Combination Expansion (Cohort 6)
  Participants will receive HC-7366 [dose selected from escalation] plus belzutifan 120 mg daily
  Interventions:

  • Drug: HC-7366
  • Drug: Belzutifan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 29, 2024): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2027
• Estimated Primary Completion Date: November 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: HiberCell; 651-675-0300; HC366-RCC2311_StudyMailbox@catalystcr.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06234605
• Other Study ID Numbers: HC366-RCC2311; MK-6482-030 ( Other Identifier: Merck Sharp & Dohme LLC )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: HiberCell, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: HiberCell, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Not Provided
• PRS Account: HiberCell, Inc.
• Verification Date: April 2024