Safety and Efficacy of TT-00420 Tablets Combined With Toripalimab Injection in Advanced Urological Tumors

NCT06221774 | Unknown Phase 1

• 1 other identifier: IUNU-PC-121
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Clear Cell Renal Carcinoma; Urothelial Carcinoma; Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (5)

• Incidence of Treatment-Emergent Adverse Events and Treatment-Related Adverse Events [Safety and Tolerability] in Phase Ib

  To assess the incidence of adverse events at different doses of TT-00420 tablets combined with Toripalimab Injection.

  Through study of Phase Ib, an average of 12 weeks

• Types of Treatment-Emergent Adverse Events and Treatment-Related Adverse Events [Safety and Tolerability] in Phase Ib

  To assess the types of adverse events at different doses of TT-00420 tablets combined with Toripalimab Injection.

  Through study of Phase Ib, an average of 12 weeks

• Severity of Treatment-Emergent Adverse Events and Treatment-Related Adverse Events [Safety and Tolerability] in Phase Ib

  To assess the severity of adverse events at different doses of TT-00420 tablets combined with Toripalimab Injection per CTCAE V5.0.

  Through study of Phase Ib, an average of 12 weeks

• ORR in Phase II

  Objective Response Rate (ORR) according to RECIST v1.1 for renal cell carcinoma, urothelial carcinoma, and prostate cancer (with baseline target lesions).

  Through study of Phase II, an average of 1 year

• PSA Response Rate in Phase II

  PSA Response Rate (including PSA50 and PSA30, per PCWG3) for prostate cancer.

  Through study of Phase II, an average of 1 year

Secondary Outcomes (11)

• 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

• DCR 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 Ib

  Through study of Phase Ib, an average of 12 weeks

Study Arms (2)

Phase Ib: dose optimization phase

EXPERIMENTAL

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.

Drug: TT-00420 + Toripalimab

Phase II

EXPERIMENTAL

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).

Drug: TT-00420 + Toripalimab

Interventions

TT-00420 + Toripalimab DRUG

TT-00420 tablets in combination with Toripalimab injection

Phase II; Phase Ib: dose optimization phase

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Failure or refusal to receive at least one systemic chemotherapy for advanced, recurrent/metastatic disease.
• Progression after one PD-1/PD-L1 inhibitor treatment.
• At least one measurable lesion (RECIST 1.1).
• Prostate Cancer:
• Pathologically confirmed mCRPC with radiologically confirmed bone metastases or soft tissue metastases.

You may not qualify if:

• \. 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).
• Active HBV infection (other abnormal HBV serology tests besides hepatitis B surface antibody positive or ≥ ULN, HBV DNA copy number required to confirm activity) and/or HCV infection (HCV RNA copy number required to confirm activity if hepatitis C virus antibody is abnormal).
• Major surgery, extensive radiotherapy within 28 days before enrollment, or local palliative radiotherapy within 2 weeks.
• Baseline: ≥ G2 peripheral neuropathy; active brain metastases, carcinomatous meningitis, spinal cord compression, or imaging studies (CT or MRI) at screening showing brain or leptomeningeal disease (patients with brain metastases who have completed treatment and stabilized symptoms within 14 days before enrollment are allowed, but must be evaluated by cranial MRI, CT, or venography to confirm no symptoms of cerebral hemorrhage).
• Factors significantly affecting oral drug absorption, such as inability to swallow, history of total gastrectomy, short bowel syndrome, or clinically significant intestinal obstruction.
• Participants who have received or are preparing to receive allogeneic bone marrow transplantation or organ transplantation.

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

Study Sites (1)

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210000, China

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma, Transitional Cell

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Hongqian Guo, PhD

CONTACT

8613605171690; dr.ghq@nju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive officer of Department of Urology, Drum Tower Hospital, Medical School of Nanjing University, Institute of Urology, Nanjing University

Study Record Dates

• First Submitted: December 24, 2023
• First Posted: January 24, 2024
• Study Start: February 1, 2024
• Primary Completion: August 31, 2025
• Study Completion: November 30, 2025
• Last Updated: January 24, 2024

Record last verified: 2024-01

Locations

CN (1)