Clinical trial NCT05808608: A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma
Official title: A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Renal Cell Carcinoma
First-line Treatment
Non Clear Cell Renal Cell Carcinoma
Sarcomatoid Renal Cell Carcinoma
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2023-04-11
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: ORR per RECIST v1.1 and imRECIST as assessed by investigators
timeFrame: 3 years
Secondary outcomes:
measure: DCR per RECIST v1.1 and imRECIST as assessed by investigators
timeFrame: 3 years
measure: OS
timeFrame: 3 years
measure: PFS per RECIST v1.1 and imRECIST as assessed by investigators
timeFrame: 3 years
measure: Life quality Questionnaire composite
timeFrame: 3 years
measure: Pain score
timeFrame: 3 years
Other outcomes:
measure: Treatment-related adverse events
timeFrame: 3 years
Locations:
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
Study officials:
affiliation: West China Hospital
name: Hao Zeng, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
citation: 2022 ASCO # Oral abstract 106.