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

Phase 1

Recruiting

• Conditions: Renal Cell Carcinoma; Non Clear Cell Renal Cell Carcinoma; First-line Treatment; Sarcomatoid Renal Cell Carcinoma
• Interventions: Drug: AK104; Drug: Axitinib

• Registration Number: NCT05808608
• Lead Sponsor: Hao Zeng

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-23
• Study First Submitted QC: 2023-04-10
• Study First Posted: 2023-04-11
• Study Start: 2023-11-17
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-22
• Last Update Posted: 2025-01-27
• Primary Completion: 2025-10
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

1. age≥18, ≤75;
2. 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 ;
3. metastatic renal cell carcinoma (TNM IV stage according to the 2009 TNM Staging system).
4. Patients who have not previously received systemic therapy, ECOG (Eastern Cooperative Oncology Group)≤2;
5. expected survival >3 months;
6. all patients signed informed consent.
7. blood routine indexes: neutrophils ≥1.5*109, platelets ≥100*109, hemoglobin ≥90g/L;
8. 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
9. 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

1. 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;
2. renal decompensation requires hemodialysis or peritoneal dialysis;
3. 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;
4. severe active clinical infection;
5. patients with coagulation disorder or bleeding constitution;
6. major surgery or severe trauma was performed within 4 weeks before enrollment;
7. a history of allogeneic organ transplantation or bone marrow transplantation;
8. drug abuse and medical, psychological or social conditions that may interfere with patients' participation in research or affect the evaluation of results;
9. known or suspected allergy to the study drug;
10. those who received treatment other than this study within 4 weeks prior to and during the study period.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination treatment group	Axitinib	Subjects in this group will receive AK104 (RP2D, administered intravenously) plus Axitinib 5 mg bid, administered orally.
Combination treatment group	AK104	Subjects in this group will receive AK104 (RP2D, administered intravenously) plus Axitinib 5 mg bid, administered orally.

Primary Outcome Measures

Name	Time	Method
ORR per RECIST v1.1 and imRECIST as assessed by investigators	3 years	ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1 and imRECIST

Secondary Outcome Measures

Name	Time	Method
PFS per RECIST v1.1 and imRECIST as assessed by investigators	3 years	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
Pain score	3 years	Evaluate pain using visual analogue scale (VAS), range from 0 to 10, higher scores predict a poor prognosis.
Life quality Questionnaire composite	3 years	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.
DCR per RECIST v1.1 and imRECIST as assessed by investigators	3 years	ORR is the proportion of subjects with complete response(CR), partial response(PR) or stable disease (SD) based on RECIST v1.1 and imRECIST
OS	3 years	OS is the time from the first use of a therapeutic drug to death from any cause

Trial Locations

Locations (1)

West China Hospital; 🇨🇳 Chengdu, Sichuan, China