A Study of HS-10516 in Patients With VHL Syndrome Associated Tumors

A Phase I Study of HS-10516 in Patients With VHL Syndrome Associated Tumors，to Investigate Safety, Tolerance, Pharmacokinetic and Efficacy

The aim of the Phase Ia portion is to identify the maximum tolerated dose or maximum acceptable dose MTD/MAD of HS-10516. The phase Ib portion will evaluate the preliminary efficacy of HS-10516 in patients with VHL Syndrome Associated Tumors.

Study Overview

• Status: Recruiting
• Conditions: Von Hippel Lindau-Deficient Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: Oral HS-10516

Detailed Description

This is a Phase Ia/Ib open label multicenter study of HS-10516 in Chinese patients aged 18 years or older with VHL Syndrome Associated Tumors. HS-10516 as a single agent, is administrated orally once daily. The aim of phase Ia, a dose escalation study, is to identify the MTD/MAD of HS-10516. The goal of Phase Ib, a dose expansion study, is to evaluate the safety, pharmacokinetics and antitumor efficacy of HS-10516.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kan Gong, PhD; Phone Number: 13910394281; Email: kan.gong@bjmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Peking University First Hospital
      • Contact: Kan Gong, PhD; Phone Number: (0086)13910394281; Email: kan.gong@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female from 18 to 80 year-old
2. Patients with advanced clear cellrenal cell carcinoma or von Hippel-Lindau Syndrome associated tumors
3. Has an Eastern Cooperative Oncology Group performance status of 0-1
4. Has a life expectancy of ≥ 12 weeks
5. Should use adequate contraceptive measures throughout the study
6. Females subject must not be pregnant at screening
7. Has the ability to understand and willingness to sign a written informed consent before the performance of the study.

Exclusion Criteria:

1. Recieved or being received treatment as follows:

   1. Hypoxia-induced factor inhibitors
   2. Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of study treatment.
   3. Cytotoxic chemotherapeutic drugs, investigational drugs or other systematic anti-tumor therapies within 3 weeks before the first dose of study treatment
   4. Colony-stimulating factors (CSFs) within 4 weeks before the first dose of study treatment
   5. Local radiotherapy within 2 weeks prior to the first dose of study treatment; more than 30% of bone marrow radiotherapy or large-area irradiation within 4 weeks before the first dose of study treatment.
   6. Major surgery within 4 weeks prior to the first dose of study treatment.
2. Has a pulse oximetry reading less than 92% at screening, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
3. Has failed to recover from a ≥ grade 2 adverse event due to prior anti-tumor therapy
4. Has another malignancy or a history of another non-VHL syndrome associated malignancy
5. Has inadequate bone marrow reserve or organ dysfunction
6. Has a clinically significant bleeding events or tendency within 1 month prior to the first dose of study treatment
7. Has severe infections within 4 weeks prior to the first dose of study treatment
8. Has digestive system diseases may influencing ADME of study drug
9. Has a history of severe hypersensitivity reaction, or proven allergic to HS-10516 or its metabolin
10. Has any disease or condition would compromise subject safety or interfere with study assessments by investigator's decision

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase Ia dose escalation arm; Participants will be assigned to pre-specified dose level to identify the MTD/MAD of HS-10516.	Drug: Oral HS-10516; Oral HIF-2α inhibitor
Experimental: Phase Ib dose expansion arm 1; Participants with VHL Syndrome associated RCC, whose lesions diameter ≤ 3 cm.	Drug: Oral HS-10516; Oral HIF-2α inhibitor
Experimental: Phase Ib dose expansion arm 2; Participants with VHL Syndrome associated RCC, who could not be included in arm 1.	Drug: Oral HS-10516; Oral HIF-2α inhibitor
Experimental: Phase Ib dose expansion arm 3; Participants with VHL Syndrome associated non-RCC tumors.	Drug: Oral HS-10516; Oral HIF-2α inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ia: MTD/MAD of HS-10516	Maximum Tolerated Dose or Maximum Acceptable Dose determined by the Number of Participants with Dose Limiting Toxicity (DLT) events during the DLT monitoring period (first 35 days of dosing) in the Dose Escalation Phase	Approximately 2 months
Phase Ib: Objective Response Rate (ORR) by Independent Review Committee (IRC)	ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR will be assessed by IRC.	Approximately 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants with Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.	Approximately 2 years
Observed maximum plasma concentration (Cmax) of HS-10516	Cmax will be obtained following administration of the first dose of HS-10516 during first 2 cycles.	Approximately 2 months
Time to reach maximum plasma concentration (Tmax) of HS-10516	Tmax will be obtained following administration of the first dose of HS-10516 during first 2 cycles.	Approximately 2 months
Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of HS-10516	Area under the plasma concentration versus time curve from time zero to the last sampling time when the concentration was no less than the lower limit of quantification (LLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.	Approximately 1 year
Overall Survival (OS)	OS defined as the time from the date the participant started study drug to death for any reason.	Approximately 2 years
ORR by investigators/IRC per system	ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Approximately 1 year
Disease Control Rate (DCR) by investigators/IRC per system	DCR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) or a stable disease (SD) of 8 weeks or longer based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Approximately 1 year
Duration of Response (DoR) by investigators/IRC per system	DoR is defined as the time from the date of first documented CR or PR, assessed by investigator and based on RECIST v. 1.1, to the documented date of progressive disease (PD) or death, whichever occurred first.	Approximately 1 year
Progression Free Survival (PFS) by investigators/IRC per system	PFS defined as the time from the date the participant started study drug to the date the participant experiences an event of disease progression or death.	Approximately 2 years

Collaborators and Investigators

• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Kan Gong, PhD, Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: August 12, 2024
• First Submitted That Met QC Criteria: August 12, 2024
• First Posted (Actual): August 14, 2024

Study Record Updates

• Last Update Posted (Actual): August 14, 2024
• Last Update Submitted That Met QC Criteria: August 12, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: RCC; pNET; VHL Syndrome; CNS hemangioblastoma; Von Hippel Lindau Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Kidney Neoplasms; Abnormalities, Multiple; Neurocutaneous Syndromes; Ciliopathies; Angiomatosis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Syndrome; Von Hippel-Lindau Disease
• Other Study ID Numbers: HS-10516-102

Drug and device information, study documents

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