Safety and Efficacy of Yiwoxidan Anti (AK112) Monotherapy in Patients With Metastatic Renal Clear Cell Carcinoma Who Are Intolerant to TKI Treatment: a Prospective, Single Arm, Phase II Clinical Study

This study is testing a new medicine called AK112 (Yivoximab) for people with advanced kidney cancer that has spread to other parts of the body (metastatic clear cell renal cell carcinoma). AK112 is a special kind of drug called a dual-target antibody that works in two ways: it helps the immune system fight cancer and blocks blood vessels that feed the tumor.

The goal of this study is to see how well AK112 works as a first-line treatment (before any other treatment) and how safe it is. We will look at how many patients' tumors shrink or stop growing, how long they live without their disease getting worse, and whether they have side effects.

This is a Phase II, single-arm, open-label study, meaning all participants will receive AK112, and everyone involved knows what treatment is being given. The study will take place at multiple hospitals across China and will include about 60 patients aged 18 to 75 years who have not received prior systemic treatment for advanced kidney cancer.

Participants will receive AK112 through an IV infusion every three weeks until the cancer progresses or side effects become too severe. They will have regular check-ups, including blood tests, imaging scans (like CT or MRI), and physical exams to monitor their health and response to treatment.

The study is expected to start in November 2023 and end in June 2027. Participation is voluntary, and all medical care related to the study will be provided at no cost. Participants may also be covered by clinical trial insurance in case of unexpected harm.

We hope this study will help find a better treatment option for people with advanced kidney cancer.

Study Overview

• Status: Enrolling by invitation
• Conditions: Metastatic Clear Cell Renal Cell Carcinoma; Renal Cell Carcinoma (RCC)
• Intervention / Treatment: Drug: Yivoximab

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 18 and 75 years, inclusive.
2. Histologically confirmed diagnosis of clear cell renal cell carcinoma (ccRCC).
3. Metastatic disease with at least one measurable lesion according to RECIST v1.1 criteria.
4. No prior systemic therapy for advanced or metastatic ccRCC.
5. ECOG Performance Status of 0 or 1.
6. Expected survival ≥12 weeks.

7. Adequate organ function:

   • Hemoglobin ≥9 g/dL
   • Absolute neutrophil count ≥1.5 × 10⁹/L
   • Platelets ≥100 × 10⁹/L
   • Total bilirubin ≤1.5 × ULN
   • AST/ALT ≤2.5 × ULN (≤5.0 × ULN if liver metastases present)
   • Serum creatinine ≤1.5 × ULN or eGFR ≥60 mL/min/1.73m²
   • INR ≤1.5 or aPTT within normal limits
8. Female patients of childbearing potential must have a negative pregnancy test at screening and agree to use effective contraception during the study and for 12 weeks after last dose.
9. Willing and able to provide written informed consent.

Exclusion Criteria:

• 1. Non-clear cell histology or mixed histology with non-clear cell component >25%.

  2. Prior treatment with PD-1/PD-L1 inhibitors, VEGF/VEGFR inhibitors, or other immune checkpoint inhibitors.

  3. Active autoimmune disease requiring systemic immunosuppressive therapy. 4. Uncontrolled hypertension (systolic BP >150 mmHg or diastolic BP >100 mmHg despite medication).

  5. Significant cardiovascular disease including unstable angina, myocardial infarction, or congestive heart failure (NYHA Class III-IV) within 6 months.

  6. Symptomatic central nervous system metastases or spinal cord compression. 7. Active infection including HBV, HCV, HIV, or active tuberculosis. 8. Known hypersensitivity to AK112 or its excipients. 9. Pregnancy or breastfeeding. 10. Any condition that may interfere with the interpretation of study results or pose an undue risk to the participant, as determined by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Yivoximab Monotherapy Arm; This arm includes patients with metastatic clear cell renal cell carcinoma who receive Yivoximab (AK112) as first-line monotherapy. The drug is administered intravenously at a dose of 20 mg/kg every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. All participants are followed for efficacy and safety outcomes, including objective response rate, progression-free survival, overall survival, and adverse events.

Drug: Yivoximab; Yivoximab (AK112) is a human IgG1κ dual-target monoclonal antibody that simultaneously binds to PD-1 and VEGF. It is administered intravenously at a dose of 20 mg/kg every 3 weeks as monotherapy. The drug is designed to enhance anti-tumor immune response by blocking immune checkpoint inhibition while inhibiting angiogenesis. This intervention is being evaluated as first-line treatment for metastatic clear cell renal cell carcinoma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The objective response rate (ORR) is defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) according to RECIST v1.1 criteria, assessed by independent radiology review. ORR will be evaluated at baseline and every 6 weeks thereafter until disease progression or withdrawal from the study. The primary endpoint will be analyzed in the intent-to-treat (ITT) population.	From study start to data cutoff date (approximately 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	The disease control rate (DCR) is defined as the proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD) for at least 6 weeks, based on RECIST v1.1 criteria. DCR will be assessed during follow-up visits and reported at the final analysis.	From study start to data cutoff date (approximately 24 months)
Overall Survival (OS)	Overall survival (OS) is defined as the time from the first dose of Yivoximab to death from any cause. OS will be estimated using the Kaplan-Meier method and reported with 95% confidence intervals. Follow-up will continue until the end of the study or until the patient is lost to follow-up.	From first dose of study drug to death from any cause, up to 36 months
Incidence of Treatment-Emergent Adverse Events (TEAEs)	TEAEs will be collected and graded according to CTCAE v5.0. Includes all AEs occurring from first dose until 30 days after last dose.	During treatment and up to 30 days after last dose
Changes in Laboratory Parameters	Hematology, chemistry, and urinalysis values will be monitored throughout the study. Abnormalities will be graded per CTCAE v5.0.	Baseline, every cycle, and at end of treatment; up to 24 months
Vital Signs Monitoring	Blood pressure, heart rate, temperature, and respiratory rate will be measured at each visit.	At screening, baseline, every cycle, and at end of treatment; up to 24 months
Concomitant Medication Use	All concomitant medications will be recorded from screening through end of study.	From screening until end of study (approximately 24 months)

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: January 19, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Clear-cell metastatic renal cell carcinoma
• Other Study ID Numbers: 2025-FXY-506

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No