Study of ST-1898 in Advanced Renal Cell Carcinoma

Advanced Renal Cell Carcinoma Clinical Trial

Official title:

A Phase Ib/II Study of ST-1898 to Evaluate the Efficacy and Safety in Patients With Renal Cell Carcinoma (RCC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06127238
• Other study ID #: ST-1898-201
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 7, 2023
• Est. completion date: December 2025

Study information

• Verified date: November 2023
• Source: Beijing Scitech-Mq Pharmaceuticals Limited
• Contact: Jun Guo, MD
• Phone: 0086-10-88121122
• Email: guoj307[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

ST-1898 is a receptor tyrosine kinase (RTK) inhibitor for multi-targets, especially for VEGFR2, c-MET, AXL，PDGFRA，RET，KIT etc. This trial is to evaluate its safety, tolerability, pharmacokinetic, and efficacy in patients with advanced renal cell carcinoma (RCC).

In phase Ib, the primary objectives are to assess the safety and tolerability, and to determine the maximum tolerated dose (MTD) of ST-1898 tablets in patients with advanced RCC. Secondary objectives are to assess the plasma concentration of ST-1898 and to evaluate the efficacy in patients with advanced RCC.

In phase II, the primary objective is to assess the anti-tumor activities of ST-1898 tablets in patients with advanced RCC. The secondary objective is to evaluate the safety of ST-1898 tablets in patients with advanced RCC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age >= 18 years

2. Life expectancy of three months or more

3. Diagnosis of advanced renal cell carcinoma (RCC) by histopathology and medical imaging, standard treatment failure or no standard treatment regimen available

4. With agreement to provide a tumor tissue specimen

5. Has the ability to understand and willingness to sign a written ICF before the performance of any study-specific procedures on this protocol

6. Has at least one measurable lesion as defined by RECIST version 1.1

7. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1

8. Has adequate organ function defined as follows:

1. Bone marrow : absolute neutrophil count = 1,500/µL, Hgb level = 90 g/L and platelet count (Plt) i. = 90x109/µL without transfusion or growth factor support within 2 weeks prior to obtaining the hematology values at screening;

2. Liver: transaminase levels (AST/ALT) = 3.0 × upper limit of normal (ULN); total bilirubin i. (TBILI) = 1.5 mg/dL in the absence of Gilbert's disease

3. Kidney: Creatinine =1.5 ULN, protein in urine =1+, if =2+ but <1g within 24h

4. Heart: LVEF=50%

5. Coagulation function: INR=1.5×ULN,APTT=1.5×ULN

9. Women of child bearing potential must have a negative serum pregnancy test within 7 days before first study drug administration. Female patients of child bearing potential, or a male patients with a female partner of child-bearing potential (defined as all women physiologically capable of becoming pregnant), must agree to use a highly effective method of contraception during screening, during the period of drug administration and for 120 days after stopping study drug administration.

Exclusion Criteria:

1. Has received another anti-tumor therapy within two weeks or within 5 half-life of anti- tumor drug prior to the first dose

2. Has had major surgery within 4 weeks before the first study drug administration (except tumor biopsy, puncture, invasive dental procedures such as tooth extraction, dental implants etc.)

3. Current or previous severe retinopathy who, in the judgment of the Investigator or specialist, are not suitable for enrollment

4. Has had any history of major cardiovascular event within 6 months prior to study drug administration including but not limited to :

1. Serious arrhythmia or cardiac conduct abnormality , such as degree II-III atrioventricular block or ventricular arrhythmia needs to be treated

2. QTc interval extension: male >450 ms, female >470 ms

3. Acute coronary syndrome, stroke, deep vein thrombosis, pulmonary- thromboembolism, arterial thrombosis, congestive heart failure, aortic dissection etc.

4. New York Heart Association Class = II

5. Has uncontrolled hypertension, as defined by a sustained blood pressure (BP) > 140/90 mHg with antihypertensive treatment

5. Has brain metastases with symptoms or with evidence of progression

6. Has Interstitial lung disease or radiation pneumonia requiring treatment by steroid

7. Has a prior or concomitant invasive malignancy other than RCC with the exception of adequately treated non-melanoma skin cancer, breast cancer in situ ,cervical carcinoma in situ or superficial bladder cancer any other malignancy from which the patient has remained disease free within the past 5 years

8. Has = grade 3 hemorrhage/bleeding event within 6 months prior to study drug administration or currently = grade 2 hemorrhage or event of high risk of hemorrhage ) including active gastritis/duodenal ulcer or esophageal varices

9. Within 2 weeks prior to study drug administration, receiving chronic concomitant treatment with strong CYP3A4 inducers or CYP3A4 inhibitors

10. Has not recovered from toxicities caused by prior therapy to CTCAE= Grade 1 (except for peripheral neuropathy becoming =Grade 2, alopecia, and other events judged tolerable by the Investigator and without safety risks).

11. Active hepatitis B (asymptomatic hepatitis B carriers with HBV DNA < 2000 IU/mL are allowed to be enrolled), hepatitis C virus (HCV) antibody-positive and HCV-RNA- positive, or other active hepatitis, clinically significant moderate-to-severe cirrhosis, are allowed to receive prophylactic antiviral therapy other than interferon.

12. Has acute bacterial, viral or fungal infections, requiring systemic anti-infective treatment.

13. HIV positive

14. Pregnant or lactating females

15. Drug or alcohol dependents

16. Has significant disorder of neurology or mental disease or poorly compliance

17. Unable to swallow oral medications or condition or conditions that in the judgment of the Investigator which severely interfere with gastrointestinal absorption, such as dysphagia, intestinal obstruction, etc.

18. Clinically uncontrollable third interstitial effusion that, in the judgment of the Investigator, is unsuitable for enrollment.

19. Has a history of other serious systemic disease, or any other reason that might interfere with participation in trial or interfere with interpretation of trial results, in the judgement of the Investigator, that are not qualified to participate in this trial.

Related Conditions & MeSH terms

• Advanced Renal Cell Carcinoma
• Carcinoma
• Carcinoma, Renal Cell

Intervention

Drug:
• ST-1898 tablets
Supplied as 5 mg and 40 mg tablets

Locations

Country	Name	City	State
China	Peking University Cancer Hospital & Institute	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Scitech-Mq Pharmaceuticals Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase Ib Dose Escalation:Maximum Tolerated Dose (MTD)	The MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first cycle (21days) of treatment.	Within the first cycle (21days)
Primary	Phase Ib Dose Escalation: The Number and frequency of treatment-related adverse events (AEs) and treatment-related serious adverse events (SAEs)	The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0.	Approximately 18 months
Primary	Phase II Expansion: Objective Response Rate (ORR)	ORR is defined as The percentage of participants who experience a CR or PR based on RECIST 1.1 (CR: Complete Response, Disappearance of all target lesions, PR: Partial Response, At least a 30% decrease in the sum of diameters of target lesions)	Approximately 18 months
Secondary	Phase Ib Dose Escalation: Plasma PK	To assess plasma pharmacokinetics (PK) of oral administration of ST-1898 in participants with advanced renal cell carcinoma	On Day 1, 8, 21 of Cycle 1 and Day 1 of Cycle 3, approximately 10 weeks
Secondary	Phase Ib Dose Escalation: ORR	Objective Response Rate (ORR) per RECIST 1.1	Approximately 18 months
Secondary	Phase Ib Dose Escalation: DOR	DOR Duration of Response (DOR) per RECIST 1.1	Approximately 18 months
Secondary	Phase Ib Dose Escalation: PFS	Progression-Free Survival (PFS) per RECIST 1.1	Approximately 18 months
Secondary	Phase Ib Dose Escalation: DCR	Disease Control Rate (DCR) per RECIST 1.1	Approximately 18 months
Secondary	Phase Ib Dose Escalation: OS	Overall Survival (OS)	Approximately 30 months
Secondary	Phase Ib Dose Escalation: TTP	Time to Progression(TTP)per RECIST 1.1	Approximately 18 months
Secondary	Phase II Dose Expansion: DOR	DOR Duration of Response (DOR) per RECIST 1.1	Approximately 18 months
Secondary	Phase II Dose Expansion: PFS	Progression-Free Survival (PFS) per RECIST 1.1	Approximately 18 months
Secondary	Phase II Dose Expansion: DCR	Disease Control Rate (DCR) per RECIST 1.1	Approximately 18 months
Secondary	Phase II Dose Expansion: OS	Overall Survival (OS) per RECIST 1.1	Approximately 30 months
Secondary	Phase II Dose Expansion: OS12m	12-Month survival rate(OS12m)	12 months
Secondary	Phase II Dose Expansion: The Number and frequency of treatment-related adverse events and serious adverse events (SAEs)	The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0.	Approximately 18 months