An Open-Label, Multi-Cohort, Two-Stage, Phase Ib/II Clinical Study to Evaluate the Safety and Efficacy of TT-00420 Tablets Combined With Toripalimab Injection in Treating Advanced Urological Tumors
Overview
- Phase
- Phase 1
- Intervention
- TT-00420 + Toripalimab
- Conditions
- Clear Cell Renal Carcinoma
- Sponsor
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events and Treatment-Related Adverse Events [Safety and Tolerability] in Phase Ib
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This Phase Ib/II clinical study is an open-label, multi-cohort, two-stage trial designed to assess the safety and efficacy of different doses of TT-00420 tablets in combination with Toripalimab injection for treating patients with advanced urological tumors. The study aims to evaluate the effectiveness of TT-00420 tablets at the optimal dose combined with Toripalimab in treating different types of advanced urological tumors.
Investigators
Hongqian Guo
Executive officer of Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Eligibility Criteria
Inclusion Criteria
- •Voluntary participation, sign the informed consent with good compliance.
- •Age between 18-80 years.
- •ECOG performance status of 0 or 1; expected survival of at least 3 months.
- •Meeting all criteria for one of the following cancer types:
- •Renal Clear Cell Carcinoma:
- •Pathologically and radiologically confirmed metastatic or unresectable advanced clear cell renal cell carcinoma.
- •Failure after at least one systemic treatment for advanced or metastatic disease (including chemotherapy, targeted therapy, immunotherapy).
- •At least one measurable lesion (RECIST 1.1).
- •Urothelial Carcinoma:
- •Pathologically and radiologically confirmed metastatic or unresectable advanced urothelial carcinoma (including bladder, ureter, renal pelvis, and urethra).
Exclusion Criteria
- •Primary pure neuroendocrine cancer (except post-treatment neuroendocrine differentiation).
- •Other antitumor treatments within 4 weeks or 5 half-lives (whichever is shorter) before the start of the study treatment (except androgen deprivation therapy for prostate cancer patients, such as LHRH agonists or antagonists, bicalutamide, flutamide, etc.), or not yet recover from the toxicity of previous treatments (except ≤ G1 adverse events or tolerable G2 alopecia, fatigue/asthenia, and neuropathy caused by trauma at baseline).
- •Concurrent diseases/history:
- •Clinically significant hemoptysis (\> 50 mL per day) within 3 months before enrollment; significant clinical bleeding symptoms or clear bleeding tendency, such as gastrointestinal bleeding, bleeding gastric ulcers, baseline fecal occult blood and above.
- •Arteriovenous thrombotic events within 6 months before enrollment, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis (except venous thrombosis caused by previous chemotherapy with venous catheterization judged by the investigator as cured), and pulmonary embolism.
- •Hypertension not well controlled with stable dose antihypertensive treatment (systolic pressure \> 150 mmHg or diastolic pressure \> 100 mmHg); myocardial infarction, severe/unstable angina, NYHA class 2 or above heart failure, clinically significant supraventricular or ventricular arrhythmias, prolonged QT interval, and symptomatic congestive heart failure within 6 months before baseline/screening.
- •Interstitial lung disease, non-infectious pneumonia, and other non-specific pneumonias (e.g., pulmonary fibrosis, interstitial pneumonia).
- •Active infection requiring antibiotic treatment within 4 weeks before the first administration of the study drug, or unexplained fever \> 38.5°C during screening or before the first administration of the study drug (fever due to tumor reasons judged by the investigator is allowed for enrollment); active tuberculosis.
- •Live attenuated vaccine vaccination history within 28 days before the first study drug administration or expected live attenuated vaccine vaccination during the study (including COVID-19 vaccine).
- •HIV infection or known acquired immunodeficiency syndrome (AIDS).
Arms & Interventions
Phase Ib: dose optimization phase
Approximately 12 participants will be enrolled and randomized 1:1 into two different dosage groups: * Dose Group A (N=6): TT-00420 tablets 10mg QD + Toripalimab 240mg Q3W. * Dose Group B (N=6): TT-00420 tablets 8mg QD + Toripalimab 240mg Q3W.
Intervention: TT-00420 + Toripalimab
Phase II
Based on the safety and efficacy data from Phase Ib, further cohorts will enroll participants with specific tumor types at the optimal dose of TT-00420 tablets: * Cohort 1 (N=10): Metastatic or unresectable advanced renal clear cell carcinoma (RCC). * Cohort 2 (N=10): Metastatic or unresectable advanced urothelial carcinoma (UC). * Cohort 3 (N=10): Metastatic castration-resistant prostate cancer (mCRPC).
Intervention: TT-00420 + Toripalimab
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events and Treatment-Related Adverse Events [Safety and Tolerability] in Phase Ib
Time Frame: Through study of Phase Ib, an average of 12 weeks
To assess the incidence of adverse events at different doses of TT-00420 tablets combined with Toripalimab Injection.
Types of Treatment-Emergent Adverse Events and Treatment-Related Adverse Events [Safety and Tolerability] in Phase Ib
Time Frame: Through study of Phase Ib, an average of 12 weeks
To assess the types of adverse events at different doses of TT-00420 tablets combined with Toripalimab Injection.
Severity of Treatment-Emergent Adverse Events and Treatment-Related Adverse Events [Safety and Tolerability] in Phase Ib
Time Frame: Through study of Phase Ib, an average of 12 weeks
To assess the severity of adverse events at different doses of TT-00420 tablets combined with Toripalimab Injection per CTCAE V5.0.
ORR in Phase II
Time Frame: Through study of Phase II, an average of 1 year
Objective Response Rate (ORR) according to RECIST v1.1 for renal cell carcinoma, urothelial carcinoma, and prostate cancer (with baseline target lesions).
PSA Response Rate in Phase II
Time Frame: Through study of Phase II, an average of 1 year
PSA Response Rate (including PSA50 and PSA30, per PCWG3) for prostate cancer.
Secondary Outcomes
- DCR in Phase II(Through study of Phase II, an average of 1 year)
- Incidence of Treatment-Emergent Adverse Events and Treatment-Related Adverse Events [Safety and Tolerability] in Phase II(Through study of Phase II, an average of 1 year)
- DCR in Phase Ib(Through study of Phase Ib, an average of 12 weeks)
- PFS in months in Phase II(Through study of Phase II, an average of 1 year)
- Types of Treatment-Emergent Adverse Events and Treatment-Related Adverse Events [Safety and Tolerability] in Phase II(Through study of Phase II, an average of 1 year)
- ORR in Phase Ib(Through study of Phase Ib, an average of 12 weeks)
- PSA Response Rate in Phase Ib(Through study of Phase Ib, an average of 12 weeks)
- OS in months in Phase Ib(Through study of Phase Ib, an average of 12 weeks)
- PFS in months in Phase Ib(Through study of Phase Ib, an average of 12 weeks)
- OS in months in Phase II(Through study of Phase II, an average of 1 year)
- Severity of Treatment-Emergent Adverse Events and Treatment-Related Adverse Events [Safety and Tolerability] in Phase II(Through study of Phase II, an average of 1 year)