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

Renal Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06049030
• Other study ID #: HS-10516-101
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: September 25, 2023
• Est. completion date: September 25, 2025

Study information

• Verified date: September 2023
• Source: Jiangsu Hansoh Pharmaceutical Co., Ltd.
• Contact: Yun Chen
• Phone: +86 18652105250
• Email: cheny22[@]hspharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 190
• Est. completion date: September 25, 2025
• Est. primary completion date: September 25, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male or female from 18 to 75 year-old

2. Histologically confirmed locally advanced or metastasis clear cell renal cell carcinoma whose standard treatment failed or proven unavailable or intolerant

3. Has at least one non-CNS target lesion per RESIST v1.1

4. Has an Eastern Cooperative Oncology Group performance status of 0-1

5. Has a life expectancy of = 12 weeks

6. Should use adequate contraceptive measures throughout the study

7. Females subject must not be pregnant at screening

8. Has the ability to understand and willingness to sign a written informed consent before the performance of the study

Exclusion Criteria:

1. Received 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 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 metabolics

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• HS-10516
Oral HIF-2a inhibitor

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Hansoh Pharmaceutical Co., Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	ORR by investigators	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
Secondary	Disease Control Rate (DCR)	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
Secondary	Duration of Response (DoR)	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
Secondary	Progression Free Survival (PFS)	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
Secondary	Overall Survival (OS)	OS defined as the time from the date the participant started study drug to death for any reason.	Approximately 2 years