A Study of HS-10516 in Patients With Advanced Clear Cell Renal Cell Carcinoma

Sponsor

Jiangsu Hansoh Pharmaceutical Co., Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06049030

Collaborator

(none)

190

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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 ccRCC.

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Carcinoma	Drug: HS-10516	Phase 1

Detailed Description

This is a Phase Ia/Ib open label multicenter study of HS-10516 in Chinese patients aged 18 years or older with advanced clear cell renal cell carcinoma who have failed or are unavailable/intolerant to standard of care. 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 Design

Study Type:

Interventional

Anticipated Enrollment :

190 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase Ia/Ib Study of HS-10516 to Investigate the Safety, Tolerance, Pharmacokinetic and Efficacy in Patients With Advanced Clear Cell Renal Cell Carcinoma

Anticipated Study Start Date :

Sep 25, 2023

Anticipated Primary Completion Date :

Sep 25, 2024

Anticipated Study Completion Date :

Sep 25, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase Ia dose escalation Participants will be assigned to pre-specified dose level to identify the MTD/MAD of HS-10516.	Drug: HS-10516 Oral HIF-2α inhibitor
Experimental: Phase Ib dose expansion arm Participants will be assigned to the recommended dose level determined in Phase Ia to evaluate the safety, pharmacokinetics and antitumor efficacy of HS-10516	Drug: HS-10516 Oral HIF-2α inhibitor

Arm

Intervention/Treatment

Experimental: Phase Ia dose escalation

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

Drug: HS-10516

Oral HIF-2α inhibitor

Experimental: Phase Ib dose expansion arm

Participants will be assigned to the recommended dose level determined in Phase Ia to evaluate the safety, pharmacokinetics and antitumor efficacy of HS-10516

Drug: HS-10516

Oral HIF-2α inhibitor

Outcome Measures

Primary Outcome Measures

Phase Ia: MTD/MAD of HS-10516 [Approximately 2 months]
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
Phase Ib: Objective Response Rate (ORR) by Independent Review Committee (IRC) [Approximately 1 year]
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.

Secondary Outcome Measures

The Number of Participants with Adverse Events [Approximately 2 years]
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.
Observed maximum plasma concentration (Cmax) of HS-10516 [Approximately 2 months]
Cmax will be obtained following administration of the first dose of HS-10516 during first 2 cycles.
Time to reach maximum plasma concentration (Tmax) of HS-10516 [Approximately 2 months]
Tmax will be obtained following administration of the first dose of HS-10516 during first 2 cycles.
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]
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.
ORR by investigators [Approximately 1 year]
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.
Disease Control Rate (DCR) [Approximately 1 year]
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.
Duration of Response (DoR) [Approximately 1 year]
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.
Progression Free Survival (PFS) [Approximately 2 years]
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.
Overall Survival (OS) [Approximately 2 years]
OS defined as the time from the date the participant started study drug to death for any reason.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female from 18 to 75 year-old
Histologically confirmed locally advanced or metastasis clear cell renal cell carcinoma whose standard treatment failed or proven unavailable or intolerant
Has at least one non-CNS target lesion per RESIST v1.1
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

Exclusion Criteria:

Received 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 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 metabolics
Has any disease or condition would compromise subject safety or interfere with study assessments by investigator's decision