Advanced Urothelial Carcinoma After Failure of Standard Therapy
Conditions
Interventions
Dose Level 2:All patients received Remimazolam (75mg, qd) combined with Toripalimab treatment and completed the 14-day DLT observation period.
Dose Level 1:All patients received Remimazolam (75mg, qod) combined with Toripalimab treatment and completed the 14-day DLT observation period.
Sponsors
Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Subjects must voluntarily agree to participate in this study, sign the informed consent form, and be willing and able to comply with all study visits and treatment plans. 2.Age =18 years, male or female. 3.Histologically confirmed disease: locally advanced or metastatic urothelial carcinoma confirmed by histology or cytology. 4.Subjects must have recently failed standard therapy and have radiographically confirmed disease progression during or after treatment. a) Standard therapy includes, but is not limited to, platinum-containing chemotherapy, PD-1/PD-L1 inhibitor monotherapy, or PD-1/PD-L1 inhibitor in combination with chemotherapy or antibody-drug conjugates (ADCs). b) Patients who have previously received PD-1/PD-L1 inhibitor therapy are allowed to enroll, except those who permanently discontinued prior immunotherapy due to immune-related adverse events. 5.At least one measurable lesion according to RECIST version 1.1. 6.Subjects must provide a qualified archival tumor tissue sample obtained within the most recent 12 months, either as a formalin-fixed paraffin-embedded block or unstained serial sections. Fresh tumor biopsy at baseline and at disease progression is strongly recommended but not mandatory for exploratory biomarker studies. Whether or not the subject agrees to biopsy will not affect eligibility for participation in the main part of this clinical trial. 7.Life expectancy =6 months. 8.Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0–1. 9.Adequate major organ function.
Exclusion criteria
Exclusion criteria: 1.History of malignancy other than urothelial carcinoma, except for either of the following conditions: a) The patient has received potentially curative treatment and has had no evidence of disease for 5 years; b) Successfully resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, or other carcinoma in situ. 2.Prior allogeneic stem cell transplantation or solid organ transplantation. 3.History of, or current diagnosis of, congenital or acquired immunodeficiency disease. 4.Known or suspected history of allergy to anti-PD-1 agents, history of hypersensitivity to chimeric or humanized antibodies or fusion proteins, or allergy to any excipients of the study drugs. 5.Other significant clinical or laboratory abnormalities that, in the investigator’s judgment, may affect safety evaluation, such as uncontrolled diabetes mellitus, chronic kidney disease, grade II or higher peripheral neuropathy according to CTCAE version 6.0, thyroid dysfunction, etc. 6.Active or poorly controlled severe infection. Active infections include: a) Positive human immunodeficiency virus (HIV) test, including HIV-1/2 antibodies; b) Active hepatitis B, defined as positive HBsAg or HBV DNA >2,000 IU/mL with abnormal liver function; c) Active hepatitis C, defined as positive HCV antibody or HCV RNA =10³ copies/mL with abnormal liver function; d) Active tuberculosis; e) Other uncontrolled active infections, CTCAE version 6.0 grade >2. 7.Incomplete recovery from surgery, such as the presence of an unhealed wound or severe postoperative complications. 8.Pregnant or breastfeeding women, or female or male patients of reproductive potential who are unwilling or unable to use effective contraceptive measures. 9.Any other condition that, in the investigator’s judgment, makes the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| RP2D of rimegepant in combination with toripalimab;Occurrence of toxicity events meeting predefined DLT criteria during the DLT observation period; | — |
Secondary
| Measure | Time frame |
|---|---|
| Radiographic progression-free survival (rPFS);adverse events; | — |
Countries
China
Contacts
Public ContactNianzeng Xing
Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Outcome results
None listed