Vorolanib Plus Sintilimab for Advanced Renal Cell Carcinoma After Failure of Prior Immune Checkpoint Inhibitors Based Combination Therapy

NCT06523049 | Not Yet Recruiting Phase 2

• 1 other identifier: VORSIN-RCC
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase II trial assesses Vorolanib and Sintilimab for advanced renal cell carcinoma after previous therapy failure. Participants receive the treatment until disease progression, intolerable side effects, death, or withdrawal. The primary endpoint is progression-free survival (PFS).

Conditions

Renal Cell Carcinoma; Immunotherapy; Molecular Targeted Therapy

Keywords

Vorolanib; Sintilimab

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-free survival is assessed by investigators based on RECIST1.1, including disease progression or death from any cause.

  3 years

Secondary Outcomes (8)

• Objective Response Rate (ORR)

  3 years

• Overall Survival (OS)

  3 years

• Adverse Events (AEs)

  3 years

• Disease Control Rate (DCR)

  3 years

• Duration of Response (DoR)

  3 years

Study Arms (1)

Combination treatment group

EXPERIMENTAL

Participants in this group will receive vorolanib tablets, 200 mg orally once daily, plus sintilimab injection, 200 mg intravenously every three weeks.

Drug: Vorolanib Tablets; Drug: Sintilimab Injection

Interventions

Vorolanib Tablets DRUG

Multi-targeted receptor tyrosine kinase inhibitor with potent inhibition of VEGFR2, KIT, PDGFR, FLT3 and RET, exerting anti-tumor effects mainly through inhibition of neovascularization.

Also known as: Vorolanib

Combination treatment group

Sintilimab Injection DRUG

Recombinant human-derived immunoglobulin G (IgG4)-type anti-programmed cell death receptor-1 (PD-1) monoclonal antibody, by binding to PD-1 and blocking PD-1 binding to PD-L1 and PD-L2, disarms the immunosuppressive effect, activates T-cell function, and enhances T-cell immunosurveillance and killing ability against tumors to generate tumor immune response.

Also known as: Sintilimab

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 years and ≤75 years, any gender.
• Histologically confirmed diagnosis of renal cell carcinoma.
• Diagnosis of metastatic renal cell carcinoma or TNM stage IV (according to the 2017 TNM staging system). Evidence of distant metastasis by imaging or pathology.
• Prior immune checkpoint inhibitors based combination therapy, dual immune combination, or immune monotherapy with disease progression, or who have received second/third line targeted monotherapy, immune monotherapy, or a change in immune-based combination therapy after failure of one of the above therapies for no more than 1 month and have completed the washout period. ECOG performance status ≤2.
• Life expectancy of at least 3 months.
• Signed informed consent and ability to comply with the protocol-specified visits and procedures.
• Agreement to provide tumor tissue and blood specimens required for the study.
• Adequate organ and bone marrow function as follows: absolute neutrophil count (ANC) ≥1×10\^9/L, platelets (PLT) ≥50×10\^9/L, hemoglobin (HGB) ≥80g/L; liver function: serum total bilirubin (TBIL) ≤3 times the upper limit of normal (ULN), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤5 times ULN, serum albumin (ALB) ≥20 g/L; renal function: serum creatinine (Cr) ≤3×ULN.

You may not qualify if:

• Pathologically diagnosed with non-renal cell carcinoma, collecting duct carcinoma.
• First-line treatment with targeted monotherapy, or progression after first-line immune checkpoint inhibitors based combination therapy, followed by more than 1 month of treatment with targeted therapies, anti-PD-1 antibodies, anti-PD-L1 antibodies, anti-PD-L2 antibodies, or anti-CTLA-4 antibodies specifically targeting T cell co-stimulation or checkpoint pathways and/or incomplete washout period.
• Active brain metastases.
• Personal history of other malignant tumors within 3 years with a different primary site or histology than that being evaluated in this study, excluding patients with well-controlled basal cell carcinoma, squamous cell carcinoma, or cervical intraepithelial neoplasia.
• Major surgery or severe trauma within 4 weeks prior to enrollment.
• Subjects with conditions requiring systemic corticosteroids (\>10mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days prior to initial study drug administration. Subjects with inactive autoimmune disease are allowed to receive local, ophthalmic, intra-articular, intranasal, inhaled corticosteroids, or adrenal replacement steroids (\>10mg/day prednisone dose or equivalent).
• Known or suspected active autoimmune disease (congenital or acquired), such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, thyroiditis, etc. Subjects with type 1 diabetes, thyroid dysfunction requiring only hormone replacement therapy, skin diseases (such as vitiligo, psoriasis, or alopecia) that do not require systemic treatment, or conditions expected not to recur in the absence of external triggering factors are allowed to participate in this study. Known allogeneic organ transplant (excluding corneal transplant) or allogeneic hematopoietic stem cell transplant.
• Allergy to any component of monoclonal antibodies.
• Uncontrolled other severe diseases, including but not limited to:
• Severe infection in the active or poorly controlled clinical phase;
• HIV infection (HIV antibody positive);
• Acute or chronic active hepatitis B (HBsAg positive and HBV DNA \>1\*103/ml) or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA \>15IU/ml);
• Active pulmonary tuberculosis, etc.
• NYHA class III-IV congestive heart failure, persistent symptomatic arrhythmia, uncontrolled atrial fibrillation; multiple echocardiographic assessments of left ventricular ejection fraction (LVEF) lower than the lower limit of normal.
• Uncontrolled hypertension (systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg);

Sponsors & Collaborators

• Hao Zeng: lead

Study Sites (1)

West China Hospital

Chengdu, Sichuan, 610000, China

Location

Related Publications (6)

• 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

• Liang C, Yuan X, Shen Z, Wang Y, Ding L. Vorolanib, a novel tyrosine receptor kinase receptor inhibitor with potent preclinical anti-angiogenic and anti-tumor activity. Mol Ther Oncolytics. 2022 Jan 10;24:577-584. doi: 10.1016/j.omto.2022.01.001. eCollection 2022 Mar 17.

  PMID: 35252556 BACKGROUND

• Pei Dong et al. , Anlotinib combined with sintilimab as first-line treatment in patients with advanced non-clear cell renal cell carcinoma (nccRR): Preliminary results from an exploratory prospective multicentre clinical study.. JCO 42, 4544-4544(2024). DOI:10.1200/JCO.2024.42.16_suppl.4544

  BACKGROUND

• Lee CH, Shah AY, Rasco D, Rao A, Taylor MH, Di Simone C, Hsieh JJ, Pinto A, Shaffer DR, Girones Sarrio R, Cohn AL, Vogelzang NJ, Bilen MA, Gunnestad Ribe S, Goksel M, Tennoe OK, Richards D, Sweis RF, Courtright J, Heinrich D, Jain S, Wu J, Schmidt EV, Perini RF, Kubiak P, Okpara CE, Smith AD, Motzer RJ. Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study. Lancet Oncol. 2021 Jul;22(7):946-958. doi: 10.1016/S1470-2045(21)00241-2. Epub 2021 Jun 15.

  PMID: 34143969 BACKGROUND

• Laccetti AL, Garmezy B, Xiao L, Economides M, Venkatesan A, Gao J, Jonasch E, Corn P, Zurita-Saavedra A, Brown LC, Kao C, Kinsey EN, Gupta RT, Harrison MR, Armstrong AJ, George DJ, Tannir N, Msaouel P, Shah A, Zhang T, Campbell MT. Combination antiangiogenic tyrosine kinase inhibition and anti-PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes. Cancer Med. 2021 Apr;10(7):2341-2349. doi: 10.1002/cam4.3812. Epub 2021 Mar 1.

  PMID: 33650321 BACKGROUND

• Iacovelli R, Ciccarese C, Procopio G, Astore S, Cannella MA, Maratta MG, Rizzo M, Verzoni E, Porta C, Tortora G. Current evidence for second-line treatment in metastatic renal cell carcinoma after progression to immune-based combinations. Cancer Treat Rev. 2022 Apr;105:102379. doi: 10.1016/j.ctrv.2022.102379. Epub 2022 Mar 12.

  PMID: 35303548 BACKGROUND

Related Links

• A Trial of Lenvatinib (E7080) Plus Pembrolizumab in Participants With Selected Solid Tumors (NCT02501096)

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

vorolanib; sintilimab

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

Study Officials

• Hao Zeng, Doctor

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hao Zeng, Doctor

CONTACT

+86-18980602129; kucaizeng@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: July 14, 2024
• First Posted: July 26, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: July 26, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• 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)