Locally advanced or advanced urothelial carcinoma that has progressed on or after prior first-line systemic therapy (including post-first-line maintenance therapy)
Conditions
Interventions
Experimental Group:Iparomlimab and Tuvonralimab combined with nab-paclitaxel
Sponsors
Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital &Institute)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.At the time of voluntarily signing the informed consent form, the subject must be aged =18 years, of any gender, and judged by the investigator as having good compliance. 2.Histopathologically confirmed urothelial carcinoma of the bladder or upper urinary tract. If other heterologous components (such as squamous cell carcinoma, adenocarcinoma, small cell carcinoma, etc.) are present, the transitional cell component must be predominant (>50%). 3.Prior first-line systemic therapy (including maintenance therapy after first-line) for unresectable locally advanced or advanced urothelial carcinoma has failed, meeting any of the following criteria: Disease progression or recurrence following first-line platinum-based regimen (e.g., cisplatin or carboplatin in combination with gemcitabine, methotrexate, vinblastine, doxorubicin, etc.) for unresectable locally advanced or advanced urothelial carcinoma. Platinum-based therapy is permitted to include combination with a PD-1 or PD-L1 inhibitor. Disease progression or recurrence following first-line PD-1 or PD-L1 inhibitor therapy for unresectable locally advanced or advanced urothelial carcinoma. 4.There is at least one measurable lesion according to RECIST v1.1 criteria. 5.Eastern Cooperative Oncology Group (ECOG, Appendix 1) performance status score of 0-1. 6.Estimated life expectancy >=3 months. 7.Adequate organ function meeting the protocol-specified laboratory criteria: hemoglobin >=90 g/L; hematological parameters: white blood cell count >=3×10^9/L, absolute neutrophil count >=1.5×10^9/L, platelet count >=100×10^9/L. 8.No organ dysfunction: total bilirubin (T-BIL) =30 mL/min (Appendix 2). 9.Male patients and female patients of childbearing potential must take adequate contraceptive measures from the time of signing the informed consent form until 6 months after the last dose of study treatment; female patients of childbearing potential must have a negative pregnancy test within 7 days prior to the first treatment.
Exclusion criteria
Exclusion criteria: 1.Women who are pregnant, planning to become pregnant, or breastfeeding. 2.History of allergy to the study drug or any of its excipients; 3.Patients with other primary malignancies within 5 years (excluding adequately treated and stable basal cell carcinoma, squamous cell skin carcinoma, cervical carcinoma in situ, etc.); 4.Severe infection occurring within 4 weeks prior to the start of study treatment, including but not limited to hospitalization due to complications of infection, bacteremia, or severe pneumonia; 5.Diagnosis of immunodeficiency, or anticipated need for systemic immunosuppressive therapy during the study treatment period, or use of systemic corticosteroids or other immunosuppressive drugs prior to the first treatment. Note: Intranasal, inhaled, or other topical corticosteroids, as well as physiological doses of systemic corticosteroids (i.e., no more than 10 mg/day of prednisone or equivalent) are not excluded. Temporary use of corticosteroids for dyspnea symptoms due to chronic obstructive pulmonary disease (COPD) or other conditions, or for allergy prophylaxis, is permitted. 6.Presence of active autoimmune disease or history of autoimmune disease, including but not limited to interstitial pneumonia, uveitis, inflammatory bowel disease, hepatitis, hypophysitis, vasculitis, systemic lupus erythematosus, etc. Note: Asymptomatic or stable hypothyroidism requiring only stable doses of hormone replacement therapy (caused by autoimmune thyroiditis) and type I diabetes mellitus requiring only stable doses of insulin replacement therapy are excluded. 7.Clinically significant cardiovascular disease: stroke (= New York Heart Association functional class II), or severe arrhythmia requiring medical therapy. 8. The following symptoms or diseases were present before the initial treatment and poorly controlled with the best treatment: (1) uncontrolled hyperglycemia (glycemic control was defined as fasting blood glucose less than 7mmol/L, current treatment with stable oral antidiabetic drugs, and stable glycemic control as assessed by a specialist); (2) patients with uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100mmHg after combined treatment of two or more antihypertensive drugs) and a history of hypertensive crisis or hypertensive encephalopathy; (3) poorly controlled malignant pleural effusion, peritoneal effusion or pericardial effusion (poorly controlled means that the volume of pleural effusion increased significantly within 2 weeks after extraction, accompanied by obvious symptoms requiring repeat puncture or other interventions); 9.Patients with a known history of human immunodeficiency virus (HIV 1/2 antibody) infection. 10.Patients with active hepatitis B or hepatitis C infection. 11.Presence of other severe and/or uncontrolled comorbidities that, in the investigator's assessment, may affect the evaluation of study safety and efficacy, or other conditions that, in the investigator's opinion, make the subject unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to Progression (TTP);Objective Response Rate (ORR);Overall Survival (OS);Disease Control Rate (DCR;Duration of Response (DoR); | — |
Countries
China
Contacts
Public ContactHui Zhang; Benkui Zou
Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital &Institute)
Outcome results
None listed