Study to Evaluate the Efficacy and Safety of Toripalimab in Combination With Axitinib Versus Sunitinib Monotherapy in Advanced Renal Cell Cancer

NCT ID: NCT04394975

Last Updated: 2025-11-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 421 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-20
• Study Completion Date: 2024-04-02

Brief Summary

This is a randomized, open-label, controlled, multicenter, phase III trial to compare the efficacy and safety of Toripalimab in combination with axitinib to sunitinib monotherapy as a first-line therapy for advanced RCC. Eligible patients will be randomized 1:1 to receive the combination therapy of Toripalimab and axitinib or sunitinib monotherapy.

Conditions

Primary Disease: Unresectable or Metastatic Renal Cell Carcinoma Focus of the Study:PFS Assessed by IRC Per RECIST 1.1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Test group

Toripalimab+axitinib combination therapy. Participants receive Toripalimab 240mg intravenously every 3 weeks plus axitinib 5mg orraly twice daily.

Group Type: EXPERIMENTAL

Biological : Toripalimab Drug: Axitinib

Intervention Type: COMBINATION_PRODUCT

Biological: Toripalimab, Intravenous infusion Drug: Axitinib, oral tablet

Control group

Sunitinib monotherapy. Participants receive sunitinib 50mg orally once daily for 4 weeks and then are off treatent for 2 weeks, or once daily for 2weeks and then are off treatent for 1 week.

Group Type: ACTIVE_COMPARATOR

sunitinib

Intervention Type: DRUG

Drug: Sunitinib, oral capsule

Interventions

Biological : Toripalimab Drug: Axitinib

Biological: Toripalimab, Intravenous infusion Drug: Axitinib, oral tablet

Intervention Type: COMBINATION_PRODUCT

sunitinib

Drug: Sunitinib, oral capsule

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Fully understand and be willing to provide written informed consent.

2. Male or female with age ≥ 18 years and <80 years.

3. Have received no prior systemic therapy after previous metastasis for RCC, histologically confirmed diagnosis of unresectable, recurrent or metastatic RCC with clear cell component with or without sarcomatoid features,Prior cytokine therapy was allowed.

4. The IDMC score was medium to high risk.

5. Having at least one measurable disease per RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if re-progression has been demonstrated.

6. Provide archival tumor tissues or newly obtained biopsies if patients participate in the exploratory study.

7. ECOG PS 0 or 1.

8. Adequate function of vital organs:

Bone marrow function (without blood or blood products transfusion, without hematopoietic stimulating factor or other medication to improve blood cell count within 2 days prior to first dose of study drug):

Absolute neutrophil count (ANC) ≥ 1.5×109/L. Platelets ≥ 100×109/L. Hemoglobin ≥ 9.0g/dL or ≥ 5.6mmol/L.

Renal function:

Serum creatinine ≤ 1.5×ULN

Hepatic function:

Serum total bilirubin ≤1.5×ULN or total bilirubin levels >1.5×ULN with direct bilirubin ≤ ULN. AST and ALT ≤2.5 × ULN, ≤5×ULN in those with hepatic metastasis.

Endocrine function:

Normal thyroid stimulating hormone, or abnormal TSH whilst normal FT3 and FT4.

Coagulation function:

International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN, and activated partial thromboplastin time (aPTT) ≤1.5×ULN, Subjects receiving anticoagulant therapy (e.g., heparin or warfarin) may participate in the study with PT or aPTT levels within the scope of the proposed therapy and monitored during study treatment.Left ventricular ejection fraction (LVEF) ≥ 50%.

8. Being willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

10. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first treatment dose. Female subjects of childbearing potential and male subjects whose partners are of childbearing potential must agree to use a highly effective methods of contraceptive throughout the study and for 180 days after the last dose of study therapy.

13. Poorly controlled hypertension (systolic blood pressure ≥ 150mmHg and/or diastolic blood pressure ≥ 90mmHg).

14. Presence of the following cardiovascular events within 6 months prior to randomization:

1. Myocardial infarction

2. Unstable angina pectoris

3. Cardiac angioplasty or stent

4. Coronary/peripheral artery bypass graft

5. Grade III or IV congestive heart failure per New York Heart Association

6. Cerebrovascular accident or transient ischemic attack

15. QT interval (QTc) ≥ 480 msec corrected with heart rate (Bazett's formula);

16. Has active hemorrhage or history of other significant hemorrhage episodes within 30 days prior to randomization.

17. Has deep vein thrombosis or pulmonary embolism within 6 months prior to randomization.

18. Has arterial thrombosis within 12 months prior to randomization.

19. Has clinically significant gastrointestinal (GI) abnormalities including:

1. Malabsorption, total gastrectomy or any other condition that might affect the absorption of orally taken medication.

2. Active ulcer under treatment in the past 6 months;

3. Active GI bleeding (e.g., hematemesis, hematochezia or melena) in the past 3 months, and without evidence of resolution documented by endoscopy or colonoscopy.

4. Intraluminal metastatic lesion with suspected hemorrhage, inflammatory bowel disease, ulcerative colitis, GI perforation, or other GI conditions associated with increased risk of perforation.

20. Has a history of or current (non-infective) pneumonia/ interstitial lung disease that required steroids.

21. Has an active infection requiring systemic therapy. Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV antibody positive), HBV or HCV infection (Patients with positive HBsAg or negative HBsAg, but positive HBcAb will be enrolled in the study when HBV DNA was tested in central laboratory and lower than ULN. Patients with a history of HCV infection may participate in the study if the result of HCV RNA test was negative during screening period).

22. Has received a live virus vaccine within 30 days prior to randomization, including (but not limited to) mumps, rubella, measles, varicella/ herpes zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guérin (BCG) and typhoid vaccine. Inactivated virus vaccines are allowed.

23. Has a history of hypersensitivity reaction, including (but not limited to) antibodies and TKIs.

24. Known history of psychiatric disorders or drug abuse.

25. Has evidence of inadequate wound healing.

26. Has current use (within 7 days of randomization) or anticipated need for treatment drugs what are known strong CYP3A4/5 inhibitor and CYP3A4/5 inducer (including, but not limited to, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin and St. John's wort) or the drugs that are known with proarrhythmic potential (including, but not limited to, terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol and benazapril, etc.).

27. Has a history or current evidence on any condition, therapy or laboratory abnormality that might confound the results of the study, interfere with subject's participation for the full duration of the study, or is not in the best interest of subject to participate, in the opinion of investigators.

Exclusion Criteria

1. PriorAnti-PD-1, PD-L1 or CTLA-4 agents ).

2. Prior systemic anti-cancer therapy after metastasis (e.g., VEGF/VEGFR or mTOR targeting agents, including (but not limited to) sunitinib, axitinib, sorafenib, pazopanib, cabozantinib, lenvatinib, bevacizumab or everolimus.

3. Progression or recurrence during neoadjuvant/adjuvant therapy for renal cell cancer or within 12 months after the last dose treatment.

4. Has participated or is currently participating in a trial of investigational agent within 4 weeks prior to the first dose of study treatment, unless observational (non-interventional) clinical study or follow-up period of interventional study.

5. Had major surgery (judged by investigators) within 4 weeks prior to the first dose of study treatment or has not recovered from prior surgery.

6. Has traditional Chinese medicine or Chinese patent medicine preparation with anti-cancer indication within 2 weeks prior to the first dose of study treatment.

7. Requiring corticosteroids (Prednisone >10 mg/day or equivalent analogue) or other immunosuppressive agents within 2 weeks prior to the first dose of study treatment. Patients without active autoimmune disease using inhaled prednisone >10 mg/day will not be excluded from the study.

8. Has a history of organ transplantation or required long-term treatment with corticosteroids.

9. Hypothyroidism, hypoadrenalism or hypopituitarism that can be controlled only with hormone replacement therapy, type I diabetes, psoriasis or leucoderma not requiring systematic treatment.

11. Has an additional malignancy that has progressed or required treatment within 5 years prior to randomization (basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ such as breast cancer, prostate cancer are acceptable if they have undergone potentially curative therapy；Remarks: Localized low-risk prostate cancer [ patietns with stage ≤ T2a, Gleason score ≤ 6 and PSA < 10ng/mL at the time of diagnosis (as measured) can be included in this study if the subject has received radical therapy and has no evidence for biochemical recurrence(PROSTATE specific antigen,PSA)].

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Junshi Bioscience Co., Ltd.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Beijing Cancer Hospital

Beijing, , China

Countries

China

References

Yan XQ, Ye MJ, Zou Q, Chen P, He ZS, Wu B, He DL, He CH, Xue XY, Ji ZG, Chen H, Zhang S, Liu YP, Zhang XD, Fu C, Xu DF, Qiu MX, Lv JJ, Huang J, Ren XB, Cheng Y, Qin WJ, Zhang X, Zhou FJ, Ma LL, Guo JM, Ding DG, Wei SZ, He Y, Guo HQ, Shi BK, Liu L, Liu F, Hu ZQ, Jin XM, Yang L, Zhu SX, Liu JH, Huang YH, Xu T, Liu B, Sun T, Wang ZJ, Jiang HW, Yu DX, Zhou AP, Jiang J, Luan GD, Jin CL, Xu J, Hu JX, Huang YR, Guo J, Zhai W, Sheng XN. Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study. Ann Oncol. 2024 Feb;35(2):190-199. doi: 10.1016/j.annonc.2023.09.3108. Epub 2023 Oct 21.

Reference Type: DERIVED

PMID: 37872020 (View on PubMed)

Other Identifiers

JS001-036-Ⅲ-RCC

Identifier Type: -

Identifier Source: org_study_id