Study of ST-1898 in Advanced Renal Cell Carcinoma

Phase 1

Recruiting

• Conditions: Advanced Renal Cell Carcinoma
• Interventions: Drug: ST-1898 tablets

• Registration Number: NCT06127238
• Lead Sponsor: Beijing Scitech-Mq Pharmaceuticals Limited

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-02-07
• Study First Submitted: 2023-10-22
• Status Verified: 2023-11
• Study First Submitted QC: 2023-11-06
• Last Update Submitted: 2023-11-06
• Study First Posted: 2023-11-13
• Last Update Posted: 2023-11-13
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ST-1898 Phase Ib	ST-1898 tablets	Dose Escalation:participants will be administered orally at 100mg,140mg,160mg,180mg, 220mg,QD during the study, until disease progression or intolerable toxicity.
ST-1898 Phase II	ST-1898 tablets	Dose Expansion: participants with advanced renal cell carcinoma will be dministered orally at recommended phase II dose from phase Ib once daily during the study, until disease progression or intolerable toxicity.

Primary Outcome Measures

Name	Time	Method
Phase Ib Dose Escalation：Maximum Tolerated Dose (MTD)	Within the first cycle (21days)	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.
Phase II Expansion: Objective Response Rate (ORR)	Approximately 18 months	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)
Phase Ib Dose Escalation: The Number and frequency of treatment-related adverse events (AEs) and treatment-related serious adverse events (SAEs)	Approximately 18 months	The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0.

Secondary Outcome Measures

Name	Time	Method
Phase Ib Dose Escalation: DCR	Approximately 18 months	Disease Control Rate (DCR) per RECIST 1.1
Phase Ib Dose Escalation: PFS	Approximately 18 months	Progression-Free Survival (PFS) per RECIST 1.1
Phase Ib Dose Escalation: DOR	Approximately 18 months	DOR Duration of Response (DOR) per RECIST 1.1
Phase Ib Dose Escalation: Plasma PK	On Day 1, 8, 21 of Cycle 1 and Day 1 of Cycle 3, approximately 10 weeks	To assess plasma pharmacokinetics (PK) of oral administration of ST-1898 in participants with advanced renal cell carcinoma
Phase Ib Dose Escalation: ORR	Approximately 18 months	Objective Response Rate (ORR) per RECIST 1.1
Phase Ib Dose Escalation: TTP	Approximately 18 months	Time to Progression（TTP）per RECIST 1.1
Phase Ib Dose Escalation: OS	Approximately 30 months	Overall Survival (OS)
Phase II Dose Expansion: DOR	Approximately 18 months	DOR Duration of Response (DOR) per RECIST 1.1
Phase II Dose Expansion: PFS	Approximately 18 months	Progression-Free Survival (PFS) per RECIST 1.1
Phase II Dose Expansion: DCR	Approximately 18 months	Disease Control Rate (DCR) per RECIST 1.1
Phase II Dose Expansion: OS	Approximately 30 months	Overall Survival (OS) per RECIST 1.1
Phase II Dose Expansion: OS12m	12 months	12-Month survival rate（OS12m）
Phase II Dose Expansion: The Number and frequency of treatment-related adverse events and serious adverse events (SAEs)	Approximately 18 months	The AEs and SAEs will be assessed according to the National Cancer Institute (NCI) CTCAE v5.0.

Trial Locations

Locations (1)

Peking University Cancer Hospital & Institute; 🇨🇳 Beijing, Beijing, China