Vorolanib Combined With Cadonilimab in the Treatment of Untreated Advanced RCC Patients

NCT06577961 | Not Yet Recruiting Phase 1

• 1 other identifier: BD-FL-IV008
• Study Type: interventional
• Target: 37
• Locations: 0 countries
• Sites: N/A

Brief Summary

Evaluate the efficacy and safety of vorolanib combined with cadonilimab in the treatment of untreated advanced RCC patients.

Conditions

Kidney Cancer; RCC; Renal Cell Carcinoma

Keywords

Kidney Cancer; RCC; Renal Cell Carcinoma; vorolanib Combined with Cadonilimab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate assessed by RECIST 1.1

  ORR, per RECIST 1.1 calculated as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR).

  12 months

Secondary Outcomes (8)

• Progression Free Survival assessed by the investigator

  24 months

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  24 months

• Overall Survival

  24 months

• Disease Control Rate

  12 months

• 12 months Progression Free Survival Rate

  12 months

Other Outcomes (1)

• Circulating Tumor Cell / circulating tumor DNA

  It is anticipated that blood tests will be conducted on patients before medication, 42±3 days after medication, and within 7 days following disease progression.

Study Arms (1)

Experimental group

EXPERIMENTAL

Vorolanib combined with cadonilimab

Drug: Vorolanib; Drug: cadonilimab

Interventions

Vorolanib DRUG

stage Ⅰ：Vorolanib 200mg QD stage Ⅱ：Vorolanib RP2D QD

Also known as: CM082

Experimental group

cadonilimab DRUG

stageⅠ：cadonilimab 10mg/kg Q3W stageⅡ：cadonilimab 10mg/kg Q3W

Also known as: AK104

Experimental 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:

• Subjects voluntarily participate in this study, willing and able to comply with and sign the informed consent form;
• Histologically confirmed clear cell renal cell carcinoma;
• Advanced (not suitable for curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC;
• No prior systemic treatment for RCC, except for the following situations:
• a) For completely resectable renal cell carcinoma, having received one type of adjuvant or neoadjuvant treatment, if the treatment does not include drugs targeting VEGF or VEGFR, and recurrence occurs at least 6 months after the last adjuvant or neoadjuvant treatment;
• Confirmed to have at least one measurable lesion according to RECIST 1.1 criteria;
• KPS score ≥ 70;
• Expected survival time of more than 3 months;
• Aged 18-75 years;
• Good function of major organs and sufficient hematology, meeting the following criteria:
• Absolute neutrophil count (ANC) ≥ 1500 cells/μL (no granulocyte colony-stimulating factor support within 2 weeks before Cycle 1, Day 1) Platelet count (PLT) ≥ 80 × 10\^9/L. WBC count ≥ 2500/μL without G-CSF, ≤ 15000/μL Lymphocyte count ≥ 500/μL Hemoglobin ≥ 9.0 g/dL (Cycle 1), not dependent on erythropoietin, and no transfusion of concentrated red blood cells (pRBC) in the past 2 weeks Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) ≤ 3 times the upper limit of normal (ULN) (liver metastasis ≤ 5 times ULN). If the patient has bone metastasis, ALP ≤ 5 times ULN.
• Serum bilirubin ≤ 1.5 × ULN. Patients with known Gilbert's syndrome can be enrolled if serum bilirubin level ≤ 3 times ULN.
• Serum albumin ≥ 2.8 g/dL Creatinine ≤ 2.0 × ULN or calculated creatinine clearance rate ≥ 30 mL/min. Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol)
• For women who are not menopausal (amenorrhea for 12 months) or surgically sterile (without ovaries and/or uterus): agree to use two appropriate methods of contraception, including at least one method with an annual failure rate of ≥ 1%.
• Sexually active subjects of childbearing potential and their partners must agree to use medically recognized contraceptive methods during the study and for 5 months after the last dose of study treatment for women and 7 months for men (e.g., barrier methods, including male condoms, female condoms, or diaphragms coated with spermicidal gel).

You may not qualify if:

• Received any systemic treatment for RCC, unless the investigator can provide evidence that the subject has been randomly assigned to the placebo group;
• Central nervous system metastasis;
• Active malignant tumor in the past 24 months (except for renal cell carcinoma, skin basal cell carcinoma or squamous cell carcinoma that has been clearly treated, as well as cervical or bladder carcinoma in situ). Participants with a history of localized and low-risk prostate cancer who have received curative treatment and have not had a prostate-specific antigen (PSA) recurrence in the past 5 years may participate in the study;
• Received prior radiotherapy within 21 days before the start of study treatment (palliative radiotherapy for bone lesions is allowed, provided it is completed at least 2 weeks before the start of study treatment);
• Currently participating in another study or received study drugs within 4 weeks before the start of study treatment.
• Receiving live vaccines within 30 days after the planned start of study treatment (first cycle/day 1). Live vaccines include but are not limited to measles, mumps, rubella, varicella/zoster (chickenpox), yellow fever, rabies, BCG, and typhoid vaccines. Injectable seasonal influenza vaccines are generally inactivated virus vaccines and are allowed; however, intranasal influenza vaccines are attenuated live vaccines and are not allowed.
• Participants with proteinuria \> 1+ on urine dipstick test will undergo a 24-hour urine collection for quantitative assessment of proteinuria. Participants with urinary protein ≥ 1g/24h will not be eligible.
• Fasting total cholesterol \> 300 mg/dL (or 7.75 mmol/L) and/or fasting triglyceride level 2.5 times the upper limit of normal (ULN). Note: These participants can be included after lipid-lowering treatment.
• Uncontrolled diabetes defined as fasting blood glucose \> 1.5 times the upper limit of normal. Note: These participants can be included after hypoglycemic treatment.
• Uncontrolled hypercalcemia (≥ 1.5 mmol/L ionized calcium or Ca ≥ 12 mg/dL or corrected serum calcium ≥ ULN) or symptomatic hypercalcemia requiring continued bisphosphonate treatment or denosumab.
• QTc interval prolongation to \> 480 ms.
• Participants who have not fully recovered from any toxicity and/or complications caused by major surgery before starting treatment.
• Malabsorption, gastrointestinal anastomosis, or any other condition that may affect the absorption of study drugs.
• Clinically significant hematuria, vomiting blood, or coughing up blood \> 0.5 teaspoon (2.5 ml) within 12 weeks before the first dose, or other significant bleeding history (such as pulmonary hemorrhage).
• Significant cardiovascular impairment within 12 months after the first dose of study drug: history of congestive heart failure New York Heart Association class II or higher, unstable angina, myocardial infarction, cerebrovascular accident, or arrhythmia related to hemodynamic instability. The following conditions are also excluded: left ventricular ejection fraction (LVEF) below the institutional normal range determined by gated blood pool scan or echocardiogram.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

vorolanib

Condition Hierarchy (Ancestors)

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

Study Officials

• xiongjun YE

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

xiongjun YE

CONTACT

+86 139 1038 0916; yexiongjun@cicams.ac.cn

xiongjun YE

CONTACT

+86 139 1038 0916

Study Design

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

Model Details: Vorolanib combined with cadonilimab

Study Record Dates

• First Submitted: July 11, 2024
• First Posted: August 29, 2024
• Study Start: August 31, 2024
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: August 29, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share