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

NCT05808608 | Recruiting Phase 1

• 1 other identifier: AK104AXI-ssRCC
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Cell Carcinoma; First-line Treatment; Non Clear Cell Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• DCR per RECIST v1.1 and imRECIST as assessed by investigators

  3 years

• OS

  3 years

• PFS per RECIST v1.1 and imRECIST as assessed by investigators

  3 years

• Life quality Questionnaire composite

  3 years

• Pain score

  3 years

Other Outcomes (1)

• Treatment-related adverse events

  3 years

Study Arms (1)

Combination treatment group

EXPERIMENTAL

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

Drug: AK104; Drug: Axitinib

Interventions

AK104 DRUG

Anti-PD-1/CTLA-4 bi-specific antibody drug; RP2D intravenously (IV)

Combination treatment group

Axitinib DRUG

An oral, small molecule, TKI selective for VEGFRs; 5mg bid orally

Combination treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hao Zeng: lead

Study Sites (1)

West China Hospital

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (4)

• 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.

  PMID: 35346519 BACKGROUND

• 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.

  PMID: 32733094 BACKGROUND

• 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.

  PMID: 29562145 BACKGROUND

• 2022 ASCO # Oral abstract 106.

  BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Axitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Hao Zeng, Professor

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hao Zeng, Professor

CONTACT

8618980602129; kucaizeng@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: March 23, 2023
• First Posted: April 11, 2023
• Study Start: November 17, 2023
• Primary Completion: October 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data would be available starting from the time when summary data are published or otherwise made available, for 3 years.
• Access Criteria: Other researchers access the data by sending an email to our PI.

Locations

CN (1)