Clinical trial NCT06049030: A Study of HS-10516 in Patients With Advanced Clear Cell Renal Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Renal Cell Carcinoma
Keywords: Advanced Clear Cell Renal Cell Carcinoma
Kidney Cancer
Renal Cancer
Recurrent Renal Cell Carcinoma
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-09-21
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase Ia: MTD/MAD of HS-10516
timeFrame: Approximately 2 months
measure: Phase Ib: Objective Response Rate (ORR) by Independent Review Committee (IRC)
timeFrame: Approximately 1 year
Secondary outcomes:
measure: The Number of Participants with Adverse Events
timeFrame: Approximately 2 years
measure: Observed maximum plasma concentration (Cmax) of HS-10516
timeFrame: Approximately 2 months
measure: Time to reach maximum plasma concentration (Tmax) of HS-10516
timeFrame: Approximately 2 months
measure: Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of HS-10516
timeFrame: Approximately 1 year
measure: ORR by investigators
timeFrame: Approximately 1 year
measure: Disease Control Rate (DCR)
timeFrame: Approximately 1 year
measure: Duration of Response (DoR)
timeFrame: Approximately 1 year
measure: Progression Free Survival (PFS)
timeFrame: Approximately 2 years
measure: Overall Survival (OS)
timeFrame: Approximately 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun Guo, M.D.
role: PRINCIPAL_INVESTIGATOR
References: