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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ST-1898 Phase Ib | Experimental | Dose Escalation:participants will be administered orally at 100mg,140mg,160mg,180mg, 220mg,QD during the study, until disease progression or intolerable toxicity. |
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| ST-1898 Phase II | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ST-1898 tablets | Drug | Supplied as 5 mg and 40 mg tablets |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Phase Ib Dose Escalation: ORR |
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Inclusion Criteria:
Age >= 18 years
Life expectancy of three months or more
Histologically and medical imaging confirmed unresectable, locally advanced or metastatic renal cell carcinoma. In Dose Escalation Phase, subjects should be progressed with standard therapy, not eligible for standard therapy or no standard therapy available;in Dose Expansion Phase, subjects should be progressed with prior immune checkpoint inhibitor and tyrosine kinase inhibitor therapy.
With agreement to provide a tumor tissue specimen
Has the ability to understand and willingness to sign a written ICF before the performance of any study-specific procedures on this protocol
Has at least one measurable lesion as defined by RECIST version 1.1
Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
Has adequate organ function defined as follows:
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:
Has received another anti-tumor therapy within two weeks or within 5 half-life of anti- tumor drug prior to the first dose
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.)
Current or previous severe retinopathy who, in the judgment of the Investigator or specialist, are not suitable for enrollment
Has had any history of major cardiovascular event within 6 months prior to study drug administration including but not limited to :
Has brain metastases with symptoms or with evidence of progression
Has Interstitial lung disease or radiation pneumonia requiring treatment by steroid
Has other malignant tumors in the last 5 years (not including non-melanoma skin cancer, breast cancer or cervical cancer in situ, and Non-Muscle-invasive bladder cancer that have been cured)
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 gastrointestinal ulcer or esophageal varices
Concomitant medication with strong inducers of CYP3A4, strong inhibitors of CYP3A4, or CYP3A4 substrates with narrow therapeutic windows within 2 weeks prior to first dose.
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).
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.
Has acute bacterial, viral or fungal infections, requiring systemic anti-infective treatment.
HIV positive
Pregnant or lactating females
Drug or alcohol dependents
Has significant disorder of neurology or mental disease or poorly compliance
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.
Clinically uncontrollable third interstitial effusion that, in the judgment of the Investigator, is unsuitable for enrollment.
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.
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| Name | Affiliation | Role |
|---|---|---|
| Jun Guo, Ph D | Peking University Cancer Hospital & Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Cancer Hospital & Institute | Beijing | Beijing Municipality | 100142 | China |
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| ID | Term |
|---|---|
| D002292 | Carcinoma, Renal Cell |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C578524 | 3-(3'-adamantan-1-yl-4'-methoxybiphenyl-4-yl)-2-propenoic acid |
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Sequential Assignment Escalation followed by Dose Expansion
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Objective Response Rate (ORR) per RECIST 1.1 |
| Approximately 18 months |
| Phase Ib Dose Escalation: DOR | DOR Duration of Response (DOR) per RECIST 1.1 | Approximately 18 months |
| Phase Ib Dose Escalation: PFS | Progression-Free Survival (PFS) per RECIST 1.1 | Approximately 18 months |
| Phase Ib Dose Escalation: DCR | Disease Control Rate (DCR) per RECIST 1.1 | Approximately 18 months |
| Phase Ib Dose Escalation: OS | Overall Survival (OS) | Approximately 30 months |
| Phase Ib Dose Escalation: TTP | Time to Progression(TTP)per RECIST 1.1 | Approximately 18 months |
| Phase II Dose Expansion: DOR | DOR Duration of Response (DOR) per RECIST 1.1 | Approximately 18 months |
| Phase II Dose Expansion: PFS | Progression-Free Survival (PFS) per RECIST 1.1 | Approximately 18 months |
| Phase II Dose Expansion: DCR | Disease Control Rate (DCR) per RECIST 1.1 | Approximately 18 months |
| Phase II Dose Expansion: OS | Overall Survival (OS) per RECIST 1.1 | Approximately 30 months |
| Phase II Dose Expansion: OS12m | 12-Month survival rate(OS12m) | 12 months |
| 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 |
| D009369 | Neoplasms |
| D007680 | Kidney Neoplasms |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |