An Exploratory Study on the Failure of Immunotherapy With Voronib Combined With Everolimus

Phase 2

Recruiting

• Conditions: Renal Cell Carcinoma Stage I
• Interventions: Drug: Volonib combined with Everolimus Formation

• Registration Number: NCT06730672
• Lead Sponsor: Sun Yat-sen University

Brief Summary

This single-arm exploratory study included patients with renal clear cell carcinoma who had previously received one type of immunotherapy and failed. The specific regimen was Voronib 200mg PO.QD combined with everolimus 5mg QD. 80 patients were planned to continue treatment until PD, toxicity became intolerable, patient withdrawal was informed, or medication had to be discontinued. Collect patient medication information and disease efficacy evaluation, adverse reactions. In this study, blood samples were collected 0-4 weeks before treatment, 2 months, 4 months, 6 months, 8 months of drug treatment, and at the time of PD progression for ctDNA detection.

Detailed Description

The participant must have received no more than two kinds of tyrosine kinase inhibitors (TKIs) medications (excluding mTOR inhibitors) and one type of immune checkpoint inhibitor treatment, with treatment failure in systemic antitumor therapy. Additionally, the participant must have completed the last systemic antitumor treatment ( chemotherapy,radiotherapy, targeted therapy, biological therapy, or endocrine therapy) at least 3 weeks prior, or at least 5 half-lives since the last systemic antitumor treatment. Furthermore, any treatment-related toxicities must have resolved to meet the laboratory test requirements for this trial.

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-02
• Study First Submitted QC: 2024-12-11
• Study First Posted: 2024-12-12
• Last Update Submitted: 2024-12-15
• Last Update Posted: 2024-12-18
• Study Start: 2024-12-30
• Primary Completion: 2027-12-27
• Study Completion: 2028-12-27

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Clear cell carcinoma of the kidney is confirmed by pathology (histology or cytology);

2. Have received systemic anti-tumor therapy with no more than 2 targeted drugs (excluding mTOR inhibitors) and 1 immune checkpoint inhibitor and failed treatment;

3. Not less than 3 weeks after receiving the last systemic anti-tumor therapy (chemotherapy, radiotherapy, targeted therapy, biotherapy or endocrine therapy), Or not less than 5 half-lives since the last systemic antitumor treatment; And treatment-related toxicity was recovered to meet the laboratory test requirements for this study;

4. ECOG score ≤ 1;

5. Over 18 years old, and less than or equal to 75 years old; a life expectancy of more than 12 weeks

6. According to RECIST 1.1 criteria: at least one measurable lesion;

7. Organ function levels must meet the following requirements:

   Bone marrow: blood test results must show hemoglobin ≥ 80 g/L, platelets ≥ 90 x 10^9/L, absolute neutrophil count ≥ 1.5 x 10^9/L; Liver: serum bilirubin ≤ 1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (if there is liver metastasis, AST and ALT ≤ 5 times the upper limit of normal are allowed); Serum creatinine < 1.5 times the upper limit of normal; Urinary protein ≤ 2+, if urinary protein > 2+, a 24-hour urine protein test must be collected with a total amount ≤ 2 grams; Well-controlled hypertensive patients; Echocardiogram shows left ventricular ejection fraction greater than 40%;

8. For women of childbearing potential, the serum pregnancy test must be negative within 7 days prior to randomization;

9. All enrolled subjects (regardless of gender) must use effective barrier contraceptive methods throughout the treatment period and for 4 weeks after treatment ends;

10. Subjects must have the ability to understand and voluntarily sign the informed consent form, and the signing of the informed consent must occur prior to any study procedure.

Exclusion Criteria

1. Previously only received single-drug targeted drug therapy against VEGF/VEGFR or mTOR；

2. Subjects currently receiving antitumor therapy (e.g., chemotherapy, radiation therapy, immunotherapy, biotherapy, hormone therapy, surgery, and/or tumor embolization, but excluding local radiation therapy for bone metastases) may be enrolled if they have a half-life of 5 years after the end of drug therapy；

3. Progression after previous mTOR therapy (monotherapy or combination)；

4. Conditions of the subjects' organ systems:

   Presence of significant pleural effusion or ascites with clinical symptoms requiring symptomatic treatment; brain metastases, or epidural metastases;

5. Subjects who have had other malignancies within the past 5 years (excluding non-melanoma skin cancer, cervical carcinoma in situ, or successfully treated basal cell carcinoma or squamous cell carcinoma);

6. Any uncontrolled clinical issues, including but not limited to, persistent or active infections, uncontrolled diabetes, decompensated liver cirrhosis;

7. Myocardial infarction, percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting, New York Heart Association (NYHA) class III/IV congestive heart failure, cerebrovascular accident, transient ischemic attack, or rest leg claudication occurring within the 12 months prior to randomization;

8. Deep vein thrombosis or pulmonary embolism occurring within 6 months prior to randomization;

9. Any major surgery performed within 4 weeks prior to randomization;

10. A clear history of mental illness that hinders understanding of the informed consent and compliance with the study protocol;

11. Patients infected with the human immunodeficiency virus (HIV);

12. Active autoimmune diseases requiring systemic treatment in the past two years (such as treatment with disease-modifying drugs, corticosteroids, or immunosuppressants);

13. Subjects known to be allergic to similar drugs;

14. Any condition affecting the subject's ability to swallow medication or any condition affecting the absorption or pharmacokinetics of the investigational drug, including any history of gastrointestinal resection or surgery;

15. The presence of severe pulmonary disease, history of asthma or COPD, and pulmonary function tests indicating moderate to severe impairment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Volonib combined with Everolimus Formation	Volonib combined with Everolimus Formation	Volonib 200mg once daily and Everolimus 5mg once daily

Primary Outcome Measures

Name	Time	Method
Progression-free survival	From date of initiate treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months until disease progression or death	The definition of Progression-free survival（PFS） is the time from the date of first dose until the first observation of disease progression (PD) (as determined by radiographic assessment) or death (whichever occurs first).

Secondary Outcome Measures

Name	Time	Method
Overall survival	From date of initiate treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months until disease progression or death	Overall survival（OS） was defined as the time from the date of first dose to the date of death from any cause.
Objective response rate	From date of initiate treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months until disease progression or death	The Objective response rate（ORR） was defined as the proportion of patients with a best overall response of complete or partial response.
Disease control rate	From date of initiate treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months until disease progression or death	Disease control rate（DCR）was defined the proportion of patients with complete response, partial response, and stable disease.
Duration of response	From date of initiate treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months until disease progression or death	Duration of response (DOR)defined as the time from first documented response, PR or CR, to progressive disease \[PD\] or death; patients who neither progressed nor died were censored on the date of their last radiographic tumor assessment.
Dynamic changes in ctDNA levels and alterations in the ctDNA mutation profile	In this study, a maximum of six blood samples were collected for ctDNA testing, specifically before treatment, and after drug treatment at 2 months, 4 months, 6 months, 8 months, and at the time of PD (progressive disease) occurrence up to 36 months	In this study, blood samples were collected for ctDNA testing.

Trial Locations

Locations (2)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China

Henan Provincial People's Hospital; 🇨🇳 Zhengzhou, Henan, China