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

Renal Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05808608
• Other study ID #: AK104AXI-ssRCC
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: September 2023
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: West China Hospital
• Contact: Hao Zeng, Professor
• Phone: 8618980602129
• Email: kucaizeng[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 33
• Est. completion date: December 2025
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 ? 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• First-line Treatment
• Renal Cell Carcinoma
• Sarcomatoid Renal Cell Carcinoma

Intervention

Drug:
• AK104
Anti-PD-1/CTLA-4 bi-specific antibody drug; RP2D intravenously (IV)
• Axitinib
An oral, small molecule, TKI selective for VEGFRs; 5mg bid orally

Locations

Country	Name	City	State
China	West China Hospital	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Hao Zeng

Country where clinical trial is conducted

China, 

References & Publications (4)

2022 ASCO # Oral abstract 106.

Diaz-Montero CM, Rini BI, Finke JH. The immunology of renal cell carcinoma. Nat Rev Nephrol. 2020 Dec;16(12):721-735. doi: 10.1038/s41581-020-0316-3. Epub 2020 Jul 30. — View Citation

Ljungberg B, Albiges L, Abu-Ghanem Y, Bedke J, Capitanio U, Dabestani S, Fernandez-Pello S, Giles RH, Hofmann F, Hora M, Klatte T, Kuusk T, Lam TB, Marconi L, Powles T, Tahbaz R, Volpe A, Bex A. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. Eur Urol. 2022 Oct;82(4):399-410. doi: 10.1016/j.eururo.2022.03.006. Epub 2022 Mar 26. — View Citation

Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Treatment-related adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, also types and degree	3 years
Primary	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
Primary	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	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
Secondary	OS	OS is the time from the first use of a therapeutic drug to death from any cause	3 years
Secondary	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
Secondary	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
Secondary	Pain score	Evaluate pain using visual analogue scale (VAS), range from 0 to 10, higher scores predict a poor prognosis.	3 years