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

NCT06553339 | Recruiting Phase 1

• 1 other identifier: HS-10516-102
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Von Hippel Lindau-Deficient Clear Cell Renal Cell Carcinoma

Keywords

Von Hippel Lindau Syndrome; VHL Syndrome; RCC; pNET; CNS hemangioblastoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• The Number of Participants with Adverse Events

  Approximately 2 years

• Observed maximum plasma concentration (Cmax) of HS-10516

  Approximately 2 months

• Time to reach maximum plasma concentration (Tmax) of HS-10516

  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

  Approximately 1 year

• ORR by investigators/IRC per system

  Approximately 1 year

Study Arms (4)

Phase Ia dose escalation arm

EXPERIMENTAL

Participants will be assigned to pre-specified dose level to identify the MTD/MAD of HS-10516.

Drug: Oral HS-10516

Phase Ib dose expansion arm 1

EXPERIMENTAL

Participants with VHL Syndrome associated RCC, whose lesions diameter ≤ 3 cm.

Drug: Oral HS-10516

Phase Ib dose expansion arm 2

EXPERIMENTAL

Participants with VHL Syndrome associated RCC, who could not be included in arm 1.

Drug: Oral HS-10516

Phase Ib dose expansion arm 3

EXPERIMENTAL

Participants with VHL Syndrome associated non-RCC tumors.

Drug: Oral HS-10516

Interventions

Oral HS-10516 DRUG

Oral HIF-2α inhibitor

Phase Ia dose escalation arm; Phase Ib dose expansion arm 1; Phase Ib dose expansion arm 2; Phase Ib dose expansion arm 3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Recieved or being received treatment as follows:
• Hypoxia-induced factor inhibitors
• Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of study treatment.
• Cytotoxic chemotherapeutic drugs, investigational drugs or other systematic anti-tumor therapies within 3 weeks before the first dose of study treatment
• Colony-stimulating factors (CSFs) within 4 weeks before the first dose of study treatment
• 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.
• Major surgery within 4 weeks prior to the first dose of study treatment.
• Has a pulse oximetry reading less than 92% at screening, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
• Has failed to recover from a ≥ grade 2 adverse event due to prior anti-tumor therapy
• Has another malignancy or a history of another non-VHL syndrome associated malignancy
• Has inadequate bone marrow reserve or organ dysfunction
• Has a clinically significant bleeding events or tendency within 1 month prior to the first dose of study treatment
• Has severe infections within 4 weeks prior to the first dose of study treatment
• Has digestive system diseases may influencing ADME of study drug
• Has a history of severe hypersensitivity reaction, or proven allergic to HS-10516 or its metabolin

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

RECRUITING

MeSH Terms

Conditions

von Hippel-Lindau Disease; Neuroectodermal Tumors, Primitive

Condition Hierarchy (Ancestors)

Neurocutaneous Syndromes; Nervous System Diseases; Angiomatosis; Vascular Diseases; Cardiovascular Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Kan Gong, PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kan Gong, PhD

CONTACT

13910394281; kan.gong@bjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2024
• First Posted: August 14, 2024
• Study Start: July 19, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2028
• Last Updated: August 14, 2024

Record last verified: 2024-08

Locations

CN (1)