Anlotinib Plus Sintilimab as First-line Treatment for Advanced Non Clear Cell Renal Cell Carcinoma

The combination of immune checkpoint inhibitors (ICIs) plus angiogenesis inhibitors has demonstrated significant anti-tumor activity in certain cancer. The goal of this study was to evaluate the efficacy and safety of sintilimab (a human programmed death-1 ICI) plus anlotinib (a multi-target tyrosine kinase inhibitor, inhibiting tumor angiogenesis and proliferative signaling) in advanced non clear cell renal cell carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Non Clear Cell Renal Carcinoma
• Intervention / Treatment: Drug: Anlotinib plus Sintilimab

• Study Type: Interventional
• Enrollment (Anticipated): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer Center, Sun Yat-sen University
      • Contact: Fang-Jian Zhou, M.D Ph.D; Phone Number: +8613922735659; Email: zhoufj@sysucc.org.cn
      • Contact: Pei Dong, M.D Ph.D; Phone Number: 13512738496; Email: dongpei@sysucc.org.cn
      • Principal Investigator: Pei Dong, M.D Ph.D
      • Principal Investigator: Xiu-Yu Cai, M.D Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects voluntarily joined the study and signed informed consent;
• Aged > 18 years;
• ECOG body status score is 0 or 1,Expected survival time is greater than 3 months.
• Locally advanced or metastatic, histological confirmed, non-clear cell RCC of all subtypes. Patients must have advanced non-clear cell of one of the following subtypes: papillary, chromophobe, collecting duct carcinoma (CDC), renal medullary carcinoma (RMC), or unclassified.
• Patients must have measurable lesions as defined by the RECIST 1.1 standard;

• Adequate hematologic and end-organ function as defined by the following laboratory results obtained within 28 days prior to the first study treatment:

  1. Absolute neutrophil count (ANC) ≥1.5x 109/L
  2. Lymphocyte count ≥ 500/uL.
  3. Platelet count ≥ 80x109/L.
  4. Hemoglobin ≥ 80 g/L (patients may be transfused to meet this criterion).
  5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) with the following exceptions: Patients with documented liver/bone metastases should have AST and ALT ≤ 5 x ULN.
  6. Serum bilirubin ≤ 1.5 x ULN.
  7. Creatinine clearance ≥ 60 mL/min.
  8. For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective forms of contraception and to continue its use 4 weeks after the last dose of anlotinib or sintilimab.
• Signed informed consent form.
• Ability and capacity to comply with study and follow-up procedures.

Exclusion Criteria:

• Those who are known to be allergic to pharmaceutical ingredients.
• Receive anti-tumor monoclonal antibody or other research drugs within 4 weeks before enrollment; have received other anti-PD-1 antibody therapy or other treatment for PD-1/PD-L1;
• Previous use of anlotinib or other angiogenesis inhibitors
• The patient has any active autoimmune disease or a history of autoimmune disease;
• There are uncontrolled heart clinical symptoms or diseases;
• Patients with congenital or acquired immune deficiency;
• Receive chemotherapy, targeted therapy, radiotherapy within 2 weeks before enrollment;
• A history of gastrointestinal perforation or major surgery within 4 weeks before enrollment;
• Overactive/venous thrombosis occurred within 6 months prior to enrollment, such as cardiovascular-cerebral vascular (including transient ischemic attack),deep vein thrombosis (except for patients who have recovered from venous catheterization due to previous chemotherapy)and pulmonary embolism;
• Those with active bleeding or bleeding tendency;
• Presence of a drug uncontrolled hypertension;
• Urine routine indicates more than urinary protein 2+;
• Correct QT interval > 470msec; if the patient has a prolonged QT interval, but the investigator's study evaluates that the prolongation is due to a cardiac pacemaker (and no other abnormalities in the heart), it is necessary to discuss with the sponsor's researcher to determine if the patient is Suitable for group study;
• Patients suspected of having other primary cancers;
• Those who are known to be allergic to pharmaceutical ingredients.
• Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening). Patients with past/resolved HBV infection (defined as having negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. A negative HBA DNA test must be obtained in patients with positive hepatitis B core antibody prior to Cycle 1 Day 1.
• Active hepatitis C infection. Patients positive hepatitis C antibody test are eligible if PCR is negative for hepatitis C viral DNA.
• Pregnant or lactating women.

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
Other: Anlotinib plus Sintilimab; Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle) .Sintilimab was administered intravenously (200mg once every 3weeks).	Drug: Anlotinib plus Sintilimab; Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle).Sintilimab was administered intravenously (200mg once every 3weeks).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival (PFS)	Time from treatment until disease progression or death	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR)	objective response rate (ORR) by RECIST1.1, the total proportion of patients with complete response (CR), partial response (PR)	up to 2 years
disease control rate (DCR)	disease control rate (DCR)by RECIST1.1, the total proportion of patients with complete response (CR), partial response (PR) and Stable Disease(SD).	up to 2 years
overall survival (OS)	Time from treatment until death from any cause	up to 2 years
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0		up to 2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Publications and helpful links

General Publications

• 1. Bray F,Ferlay J,Soerjomatarm I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424. 2. Choueiri T,Motzer R.Systemic therapy for metastatic renal-cell carcinoma[J].N Engl J Med,2017,376(4):354-366 3. ESCUDIER B,EISEN T,STADLER W M,et al.Sorafenib in advanced clear cell renal-cell carcinoma[J].N Engl J Med,2007,356(2):125-134 4. MOTZER R J,HUTSON T E,TOMCZAK P,et al.Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma[J].J Clin Oncol,2009,27(22):3584-3590 5. Armstrong AJ, Halabi S, Eisen T, et al. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol. 2016;17(3):378-388. 6. Nizar M Tannir, Eric Jonasch, Laurence Albiges, et al. Everolimus Versus Sunitinib Prospective Evaluation in Metastatic Non-Clear Cell Renal Cell Carcinoma (ESPN): A Randomized Multicenter Phase 2 Trial[J]. European Urology, 2016, 69(5):866-874. 7. Motzer RJ, Barrios CH, Kim TM, et al.: Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and secondline everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol 2014; 32:2765-2772. 8. Zhou AP,Bai Y,Song Y,et al. Anlotinib Versus Sunitinib as First-Line Treatment for Metastatic Renal Cell Carcinoma:A Randomized PhaseⅡClinical Trial[J]. Oncologist,2019,24(8):e702-e708. DOI:10.1634/theoncologist.2018-0839. 9. CHOUEIRI T K,FISHMAN M N,ESCUDIER B,et al.Immunomodulatory activity of nivolumab in metastatic renal cell carcinoma[J].Clin Cancer Res,2016,22(22):5461-5471. 10. MCDERMOTT D F,SOSMAN J A,SZNOL M,et al.Atezolizumab,an antiprogrammed death-ligand 1 antibody,in metastatic renal cell carcinoma:long-term safety,clinical activity,and immune correlates from a phase Ⅰa study[J].J Clin Oncol,2016,34(8):833-842. 11. Rini, BI; Plimack, ER; Stus, V; et al.Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma.[J].N Engl J Med.2019,380(12):1116-1127 12. YASUDA S,SHO M,YAMATO I,et al.Simultaneous blockade of programmed death 1 and vascular endothelial growth factor receptor 2 (VEGFR2) induces synergistic anti-tumour effect in vivo[J].Clin Exp Immunol,2013,172:500-506

Study record dates

Study Major Dates

• Study Start (Anticipated): February 28, 2022
• Primary Completion (Anticipated): December 30, 2024
• Study Completion (Anticipated): December 30, 2024

Study Registration Dates

• First Submitted: December 24, 2021
• First Submitted That Met QC Criteria: February 1, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): February 2, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: SL-B2021-245-02

Drug and device information, study documents

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