Anlotinib Plus Sintilimab as First-line Treatment for Advanced Non Clear Cell Renal Cell Carcinoma

Study Overview
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Brief Summary
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The combination of immune checkpoint inhibitors (ICIs) plus angiogenesis inhibitors has demonstrated significant anti-tumor activity in certain cancer. The goal of this study was to evaluate the efficacy and safety of sintilimab (a human programmed death-1 ICI) plus anlotinib (a multi-target tyrosine kinase inhibitor, inhibiting tumor angiogenesis and proliferative signaling) in advanced non clear cell renal cell carcinoma.

Official Title
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Anlotinib Plus Sintilimab as First-line Treatment for Advanced Non Clear Cell Renal Cell Carcinoma

Conditions
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Non Clear Cell Renal Carcinoma

Intervention / Treatment
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* Drug: Anlotinib plus Sintilimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects voluntarily joined the study and signed informed consent; Aged > 18 years; ECOG body status score is 0 or 1,Expected survival time is greater than 3 months. Locally advanced or metastatic, histological confirmed, non-clear cell RCC of all subtypes. Patients must have advanced non-clear cell of one of the following subtypes: papillary, chromophobe, collecting duct carcinoma (CDC), renal medullary carcinoma (RMC), or unclassified. Patients must have measurable lesions as defined by the RECIST 1.1 standard; Adequate hematologic and end-organ function as defined by the following laboratory results obtained within 28 days prior to the first study treatment: Absolute neutrophil count (ANC) ≥1.5x 109/L Lymphocyte count ≥ 500/uL. Platelet count ≥ 80x109/L. Hemoglobin ≥ 80 g/L (patients may be transfused to meet this criterion). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) with the following exceptions: Patients with documented liver/bone metastases should have AST and ALT ≤ 5 x ULN. Serum bilirubin ≤ 1.5 x ULN. Creatinine clearance ≥ 60 mL/min. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective forms of contraception and to continue its use 4 weeks after the last dose of anlotinib or sintilimab. Signed informed consent form. Ability and capacity to comply with study and follow-up procedures. Exclusion Criteria: Those who are known to be allergic to pharmaceutical ingredients. Receive anti-tumor monoclonal antibody or other research drugs within 4 weeks before enrollment; have received other anti-PD-1 antibody therapy or other treatment for PD-1/PD-L1; Previous use of anlotinib or other angiogenesis inhibitors The patient has any active autoimmune disease or a history of autoimmune disease; There are uncontrolled heart clinical symptoms or diseases; Patients with congenital or acquired immune deficiency; Receive chemotherapy, targeted therapy, radiotherapy within 2 weeks before enrollment; A history of gastrointestinal perforation or major surgery within 4 weeks before enrollment; Overactive/venous thrombosis occurred within 6 months prior to enrollment, such as cardiovascular-cerebral vascular (including transient ischemic attack),deep vein thrombosis (except for patients who have recovered from venous catheterization due to previous chemotherapy)and pulmonary embolism; Those with active bleeding or bleeding tendency; Presence of a drug uncontrolled hypertension; Urine routine indicates more than urinary protein 2+; Correct QT interval > 470msec; if the patient has a prolonged QT interval, but the investigator's study evaluates that the prolongation is due to a cardiac pacemaker (and no other abnormalities in the heart), it is necessary to discuss with the sponsor's researcher to determine if the patient is Suitable for group study; Patients suspected of having other primary cancers; Those who are known to be allergic to pharmaceutical ingredients. Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening). Patients with past/resolved HBV infection (defined as having negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. A negative HBA DNA test must be obtained in patients with positive hepatitis B core antibody prior to Cycle 1 Day 1. Active hepatitis C infection. Patients positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Anlotinib plus Sintilimab<br>Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle) .Sintilimab was administered intravenously (200mg once every 3weeks). | Drug: Anlotinib plus Sintilimab<br>* Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle).Sintilimab was administered intravenously (200mg once every 3weeks).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) | Time from treatment until disease progression or death | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate (ORR) | objective response rate (ORR) by RECIST1.1, the total proportion of patients with complete response (CR), partial response (PR) | up to 2 years | 
| disease control rate (DCR) | disease control rate (DCR)by RECIST1.1, the total proportion of patients with complete response (CR), partial response (PR) and Stable Disease(SD). | up to 2 years | 
| overall survival (OS) | Time from treatment until death from any cause | up to 2 years | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 |  | up to 2 years |