A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma

Study Overview
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Brief Summary
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This is a Phase Ib/II, open-label, single arm trial to evaluate the efficacy and safety of AK104 in combination with axitinib as a first-line treatment for advanced/metastatic special pathological subtypes of renal cell carcinoma (ssRCC). Subjects will receive AK104 plus axitinib until disease progression, development of unacceptable toxic effects, death, a decision by the physician or patient to withdraw from the trial. The primary endpoint is ORR and PFS per RECIST v1.1 and imRECIST as assessed by investigators.

Official Title
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A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma

Conditions
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Renal Cell Carcinoma, First-line Treatment, Non Clear Cell Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma

Intervention / Treatment
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* Drug: AK104
* Drug: Axitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age≥18, ≤75; histology characteristics accord with special pathological subtypes of RCC: papillary renal cell carcinoma, chromophobic cell carcinoma, TFE3 rearrangement renal cell carcinoma, FH-deficient renal cell carcinoma, collecting duct carcinoma, medullary carcinoma, sarcomatoid carcinoma (>10%), unclassified renal cell carcinoma ; metastatic renal cell carcinoma (TNM IV stage according to the 2009 TNM Staging system). Patients who have not previously received systemic therapy, ECOG (Eastern Cooperative Oncology Group)≤2; expected survival >3 months; all patients signed informed consent. blood routine indexes: neutrophils ≥1.5*109, platelets ≥100*109, hemoglobin ≥90g/L; liver function: bilirubin ≤ normal upper limit 1.5 times, ALT/AST≤ normal upper limit 2.5 times;Serum creatinine ≤ 1.5 times of normal upper limit the following diseases did not appear within 12 months: myocardial infarction, severe or unstable angina pectoris, asymptomatic heart failure, cardiovascular and cerebrovascular accident or transient ischemic attack, etc. Exclusion Criteria: other malignancies previously or at the same time that are different from the primary site or histology of the tumor assessed in this study, except cervical carcinoma in situ, basal-cell carcinoma that has been fully treated, superficial bladder tumor (Ta, Tis, T1) or other malignancies that occurred before the enrollment and have been cured for more than 3 years; renal decompensation requires hemodialysis or peritoneal dialysis; arrhythmia need anti-arrhythmic treatment, symptomatic coronary artery disease or myocardial ischemia (myocardial infarction), nearly six months, or congestive heart failure than NYHA Ⅱ level; Hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg) that has been treated with 2 or more antihypertensive treatments and still cannot be controlled; severe active clinical infection; patients with coagulation disorder or bleeding constitution; major surgery or severe trauma was performed within 4 weeks before enrollment; a history of allogeneic organ transplantation or bone marrow transplantation; drug abuse and medical, psychological or social conditions that may interfere with patients' participation in research or affect the evaluation of results; known or suspected allergy to the study drug; those who received treatment other than this study within 4 weeks prior to and during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Experimental: Combination treatment group<br>Subjects in this group will receive AK104 (RP2D, administered intravenously) plus Axitinib 5 mg bid, administered orally. | Drug: AK104<br>* Anti-PD-1/CTLA-4 bi-specific antibody drug; RP2D intravenously (IV)<br>Drug: Axitinib<br>* An oral, small molecule, TKI selective for VEGFRs; 5mg bid orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR per RECIST v1.1 and imRECIST as assessed by investigators | ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1 and imRECIST | 3 years | 
| 12-month PFS rate per RECIST v1.1 and imRECIST as assessed by investigators | Progression is assessed by investigators based on RECIST v1.1 and imRECIST, including disease progression or death from any cause. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DCR per RECIST v1.1 and imRECIST as assessed by investigators | ORR is the proportion of subjects with complete response(CR), partial response(PR) or stable disease (SD) based on RECIST v1.1 and imRECIST | 3 years | 
| OS | OS is the time from the first use of a therapeutic drug to death from any cause | 3 years | 
| PFS per RECIST v1.1 and imRECIST as assessed by investigators | PFS is the time from the first use of a therapeutic drug to disease progression or death from any cause, progression is assessed by investigators based on RECIST v1.1 and imRECIST | 3 years | 
| Life quality Questionnaire composite | Evaluate life quality using EuroQol Five Dimensions Questionnaire (EQ-5D). EQ-5D included two aspects: EQ-5D Descriptive System and the EQ-5D visual analogue scale (EQ-VAS). In the description system, health status will be evaluated in 5 aspects: Mobility, Self-care, Usual Activities, Pain/Discomfort, Anxiety/Depression. EQ-VAS ranges from 0 to 100, higher scores indicate better health. | 3 years | 
| Pain score | Evaluate pain using visual analogue scale (VAS), range from 0 to 10, higher scores predict a poor prognosis. | 3 years |