Title
A Phase 1b, Open-Label, Safety, Tolerability, and Efficacy Study of HC7366 in Combination with Belzutifan (WELIREG TM) in Patients with Locally Advanced or Metastatic Renal Cell Carcinoma

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

Objective
Primary:
-- 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 (combination only).

Secondary:
-- To preliminarily assess the potential antitumor activity of HC-7366 in terms of response rate, disease stabilization, and survival outcomes by assessing:
1. Overall response rate (ORR) per RECIST v1.1
2. Duration of response (DOR; CR or PR) or stable disease
3. Time to Response (TTR)
4. Median progression free survival (PFS) and PFS at six months
5. Median overall survival (OS) and 1-yr OS

--To determine the plasma concentration and PK parameters of HC-7366 following single and multiple doses of HC-7366 alone or in combination with belzutifan administered to patients with locally advanced (inoperable) or metastatic RCC with predominantly clear cell histology, irrespective of VHL gene mutation status (PK parameters of both HC-7366 and belzutifan will be measured).

--To characterize HC-7366 monotherapy safety and efficacy in RCC patients within the same study as the combination of HC-7366 and belzutifan (specifically at the same centers and under the same inclusion and exclusion criteria) (Monotherapy only based on primary endpoints related to safety and tolerability outlined in sub-bullets 2-6).

Treatment 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.

Key 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

Applicable Disease Sites
Kidney

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital