Clinical trial NCT06127238: Study of ST-1898 in Advanced Renal Cell Carcinoma
Official title: A Phase Ib/II Study of ST-1898 to Evaluate the Efficacy and Safety in Patients With Renal Cell Carcinoma (RCC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Renal Cell Carcinoma
Keywords: ST-1898, renal cell carcinoma
Lead sponsor: Beijing Scitech-Mq Pharmaceuticals Limited
Sponsor class: INDUSTRY
First posted: 2023-11-13
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Sequential Assignment Escalation followed by Dose Expansion
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase Ib Dose Escalation：Maximum Tolerated Dose (MTD)
timeFrame: Within the first cycle (21days)
measure: Phase Ib Dose Escalation: The Number and frequency of treatment-related adverse events (AEs) and treatment-related serious adverse events (SAEs)
timeFrame: Approximately 18 months
measure: Phase II Expansion: Objective Response Rate (ORR)
timeFrame: Approximately 18 months
Secondary outcomes:
measure: Phase Ib Dose Escalation: Plasma PK
timeFrame: On Day 1, 8, 21 of Cycle 1 and Day 1 of Cycle 3, approximately 10 weeks
measure: Phase Ib Dose Escalation: ORR
timeFrame: Approximately 18 months
measure: Phase Ib Dose Escalation: DOR
timeFrame: Approximately 18 months
measure: Phase Ib Dose Escalation: PFS
timeFrame: Approximately 18 months
measure: Phase Ib Dose Escalation: DCR
timeFrame: Approximately 18 months
measure: Phase Ib Dose Escalation: OS
timeFrame: Approximately 30 months
measure: Phase Ib Dose Escalation: TTP
timeFrame: Approximately 18 months
measure: Phase II Dose Expansion: DOR
timeFrame: Approximately 18 months
measure: Phase II Dose Expansion: PFS
timeFrame: Approximately 18 months
measure: Phase II Dose Expansion: DCR
timeFrame: Approximately 18 months
measure: Phase II Dose Expansion: OS
timeFrame: Approximately 30 months
measure: Phase II Dose Expansion: OS12m
timeFrame: 12 months
measure: Phase II Dose Expansion: The Number and frequency of treatment-related adverse events and serious adverse events (SAEs)
timeFrame: Approximately 18 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital & Institute
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun Guo, Ph D
role: PRINCIPAL_INVESTIGATOR
References: