A Study of Toripalimab in Adjuvant Therapy After Resection of High-risk Renal Cancer

Phase 2Active Not RecruitingNCT06584435

Tianjin Medical University Second Hospital100 enrolled

Overview

The goal of this clinical trial is to learn if the drug toripalimab (an anti-PD-1 antibody) works to prevent cancer recurrence in patients with high-risk renal cell carcinoma after they have had surgery to remove the kidney (nephrectomy). The study will also learn about the safety of toripalimab in this setting.The main questions the study aims to answer are: 1. Does treatment with toripalimab after nephrectomy increase the time patients live without their cancer returning (disease-free survival) compared to what would be expected without this treatment? 2. What medical problems (side effects) do participants have when receiving toripalimab? This is a single-arm study, meaning all participants in the trial will receive the study drug, toripalimab.. Researchers will monitor participants over time to see if the outcomes with toripalizumab are better than what is historically known for similar patients who only had surgery. Participants in this study will: 1. Receive toripalimab by intravenous (IV) infusion once every 3 weeks for up to about one year ( 17 doses). 2. Visit the clinic regularly for check-ups, which will include: Imaging scans (like CT or MRI) of the chest, abdomen, and pelvis every 12 weeks to check for cancer recurrence. Blood and urine tests to monitor safety. Questionnaires about their quality of life and symptoms. Be followed for a long period after treatment ends to track overall survival and long-term health.

1. Study Background and Rationale Renal cell carcinoma (RCC) carries a substantial risk of recurrence post-nephrectomy, particularly in patients with intermediate-high risk, high risk, or M1 no evidence of disease (NED) status following metastasectomy. The phase III KEYNOTE-564 clinical trial demonstrated that adjuvant therapy with pembrolizumab, an anti-PD-1 antibody, significantly improved disease-free survival (DFS) compared to placebo in this patient population, establishing a new therapeutic standard. Building upon this landmark finding, the present study aims to investigate the efficacy and safety of toripalimab, another anti-PD-1 monoclonal antibody, within a similar clinical context. This single-arm, phase II trial seeks to evaluate whether toripalimab can provide comparable clinical benefits, including reduced recurrence risk and improved survival outcomes, for patients with high-risk RCC following complete surgical resection, while thoroughly assessing its safety profile. 2. Study Objectives Primary Objectives: To evaluate the efficacy of adjuvant toripalimab as measured by investigator-assessed Disease-Free Survival (DFS) and Overall Survival (OS). Secondary Objectives: To assess the safety and tolerability profile of adjuvant toripalimab and patient-reported outcomes (PROs) using quality of life questionnaires.. 3. Trial Design and Methodology This is a single-center, prospective, single-arm, Phase II clinical trial. The design leverages the positive signal observed in the KEYNOTE-564 trial to explore the potential of a similar immunotherapeutic agent, toripalimab, in a real-world setting at a major academic center. The study will enroll patients who have undergone nephrectomy and are within the 4 to 12-week postoperative window. Treatment involves intravenous administration of toripalimab at a fixed dose of 240 mg every three weeks, for a planned treatment duration of approximately one year (17 cycles), mirroring the treatment schedule found effective in the precedent trial. Treatment will continue until disease recurrence, unacceptable toxicity, or other protocol-defined discontinuation criteria are met. The single-arm design is chosen to efficiently characterize the activity and safety of toripalimab in this specific adjuvant setting, with outcomes referenced against historical controls and the results of prior pivotal studies. 4. Study Procedures and Assessments The assessment schedule is structured to closely monitor for efficacy and safety signals, consistent with the standards set by recent practice-changing trials. Key procedures include: Screening Period (Within 4 weeks prior to treatment initiation): * Informed consent process. * Confirmation of diagnosis and high-risk status via central pathology review . * Tumor imaging via CT or MRI of the chest, abdomen, and pelvis to confirm no evidence of disease post-surgery. * Collection of archival tumor tissue from nephrectomy/metastasectomy. * Physical examination, vital signs, ECOG performance status assessment. * Clinical laboratory tests: hematology, serum chemistry, thyroid function, coagulation profile, urinalysis. * Viral serology testing (HBV, HCV, HIV). * Pregnancy test for women of childbearing potential (WOCBP). * Baseline quality of life assessments (EORTC QLQ-C30 and FKSI-15). Treatment Period (Each cycle is 3 weeks): * Pre-dose assessments (Day 1 of each cycle): Vital signs, directed physical exam, assessment of adverse events (AEs) and concomitant medications. * Toripalimab administration: IV infusion on Day 1 of each cycle. * Laboratory tests: Hematology and serum chemistry at every cycle; urinalysis and thyroid function tests periodically as specified in the protocol. * Tumor imaging: CT/MRI scans of chest, abdomen, and pelvis will be performed every 12 weeks (± 7 days) from the date of treatment to assess for disease recurrence. * Quality of Life (QoL) assessments: EORTC QLQ-C30 and FKSI-15 questionnaires will be administered at predefined cycles and at the end of treatment. Post-Treatment Follow-up Period: * Safety Follow-up Visit: Occurs 30 days (± 7 days) after the last dose of toripalimab for ongoing AE monitoring. * Efficacy Follow-up: After treatment discontinuation (without disease recurrence), patients will continue tumor imaging assessments every 12 weeks (Year 1-3), then every 24 weeks (Years 4+) until disease recurrence, start of new anticancer therapy, or study end. * Survival Follow-up: Overall survival status will be assessed via telephone or clinic visit every 12 weeks (± 7 days) until death, withdrawal of consent, or the end of the study. 5. Endpoints The endpoints are selected to align with the established efficacy parameters in adjuvant RCC immunotherapy trials, facilitating a meaningful evaluation of toripalimab's benefit-risk profile. Primary Endpoint: * Disease-Free Survival (DFS) , defined as the time from randomization to the first documented local or distant recurrence or death from any cause. * Overall Survival (OS): Defined as the time from randomization to death from any cause. Secondary Endpoints: Include incidence and severity of adverse events (AEs/SAEs) graded by CTCAE v5.0, and changes from baseline in PRO scores. 6. Statistical Considerations The sample size is planned to be 40-100 participants. The analysis will be primarily descriptive for this single-arm study. Efficacy analyses (DFS, OS) will be performed on the Full Analysis Set (FAS) using Kaplan-Meier methodology. Safety analyses will be conducted on the Safety Set (SS). The results will be contextualized with reference to existing data from the adjuvant RCC treatment landscape, including findings from the KEYNOTE-564 trial.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

1. INCLUSION CRITERIA Participants must meet ALL of the following criteria to be eligible for study enrollment: 1.1 Informed Consent Capable of giving signed informed consent； Willing to comply with all study procedures； Signed and dated written informed consent obtained prior to any study-specific procedures. 1.2 Age and Sex Age ≥18 years at time of consent； Male and female participants eligible. 1.3 Disease Characteristics Histologically confirmed renal cell carcinoma with clear cell component; Must have undergone nephrectomy with complete resection; No evidence of residual tumor confirmed by imaging; Must meet at least ONE of the following high-risk criteria: pT2,with Fuhrman Grade IV or sarcomatoid,N0,M0;pT3/4,N0M0 (any grade);Any T classification with N1,M0;Post nephrectomy(total/partial) plus complete resection of metastasis, M1 NED. 1.4 Brain Metastasis No suspected or confirmed active brain metastases. 1.5 Performance Status Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 1.6 Organ Function (within 14 days prior to enrollment, without transfusion or growth factor support) Hematopoietic function: Absolute neutrophil count ≥1,500/mm³; Platelet count ≥100,000/mm³; Hemoglobin ≥9.0 g/dL (5.6 mmol/L) Hepatic function: Total bilirubin ≤1.5 × ULN; AST and ALT ≤1.5 × ULN Renal function: Serum creatinine ≤1.5 mg/dL; OR creatinine clearance ≥60 mL/min (Cockcroft-Gault formula) 1.7 Contraception Females of childbearing potential must use medically approved contraception during treatment and for 3 months after last dose; Negative serum or urine pregnancy test within 7 days prior to randomization for women of childbearing potential; Non-lactating females; Males with female partners of childbearing potential must use effective contraception during treatment and for 3 months after last dose 1.8 Compliance Voluntarily agrees to participate by signing informed consent; Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures 2. EXCLUSION CRITERIA Participants meeting ANY of the following criteria will be excluded from study participation: 2.1 Prior Therapy Previous radiotherapy, chemotherapy, targeted therapy, long-term or high-dose hormone therapy, or any immune checkpoint inhibitor treatment. 2.2 Concurrent Malignancy History of or current concurrent malignancy (except adequately treated basal cell carcinoma of skin, carcinoma in situ of cervix, etc.). 2.3 Allergy and Prior Immunotherapy Previous treatment with other PD-1/PD-L1 inhibitors; Known hypersensitivity to macromolecular protein preparations or any PD-1 inhibitor components. 2.4 Autoimmune Disease Active autoimmune disease or history of autoimmune disease; Exceptions:Controlled type 1 diabetes, hypothyroidism requiring only hormone replacement, skin diseases not requiring systemic treatment (vitiligo, psoriasis), or childhood asthma in complete remission without intervention in adulthood. 2.5 Immunosuppressive Therapy Current use of immunosuppressants (e.g., systemic corticosteroids \>10 mg/day prednisone equivalent) for immunosuppressive purposes, continued within 2 weeks prior to enrollment. 2.6 Cardiovascular Disease Poorly controlled cardiac clinical symptoms or diseases, including: NYHA Class II or higher heart failure; Unstable angina pectoris; Myocardial infarction within 1 year; Clinically significant arrhythmias requiring treatment 2.7 Coagulation Function Abnormal coagulation function with bleeding tendency; Current thrombolytic or anticoagulant therapy; 2.8 Gastrointestinal Disease Current active gastrointestinal diseases including: Esophageal varices; Active ulcers; Inflammatory bowel disease; Risk of perforation or bleeding; 2.9 Hemorrhage and Thrombosis Events History of or current severe hemorrhage, hemoptysis, or thrombotic events within 12 months. 2.10 Infection Active infection requiring systemic therapy; Unexplained fever \>38.5°C during screening or before first dose; Congenital or acquired immunodeficiency, including HIV infection or active hepatitis 2.11 Other Medical Conditions History of severe pulmonary fibrosis, interstitial pneumonia, radiation pneumonia; Live vaccination within 4 weeks prior to study treatment; History of psychotropic drug abuse, alcoholism, or drug addiction 2.12 Administrative Reasons Participation in another clinical study or within 1 month after completion of previous clinical study; Any condition that, in the investigator's judgment, may lead to early study termination affecting participant safety or data quality 3. WITHDRAWAL CRITERIA Participants will be withdrawn from study treatment if ANY of the following occurs: 3.1 Participant Request Participant or legal representative requests withdrawal 3.2 Disease Progression Confirmed disease progression 3.3 Intolerable Toxicity Occurrence of intolerable toxicities 3.4 Investigator Judgment Investigator determines continued participation may harm the participant 3.5 Protocol Violations Pregnancy Loss to follow-up Major protocol violation 3.6 Treatment Delay Any cause leading to treatment delay \>2 weeks.

Outcomes

Primary Outcomes

Disease-Free Survival (DFS) as Assessed by Investigator

Disease-Free Survival is defined as the time from enrollment to the first documented occurrence of any of the following events: Local recurrence of renal cell carcinoma (confirmed by imaging) Distant metastasis of renal cell carcinoma (confirmed by imaging) Death from any cause Participants without documented DFS events at the time of analysis will be censored at the date of their last tumor assessment. Tumor assessments will be performed using computed tomography (CT) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines.

Time frame: From enrollment until the first documented disease recurrence, distant metastasis, or death from any cause (whichever occurs first), assessed up to 60 months

Secondary Outcomes

Overall Survival (OS)

Overall Survival is defined as the time from enrollment to death from any cause. Participants who are alive at the time of analysis will be censored at the last known alive date. Survival status will be collected through regular follow-up contacts every 12 weeks (± 7 days) until death, withdrawal of consent, or the end of the study, whichever occurs first.

Time frame: From enrollment until death from any cause, assessed up to 120 months

Incidence and Severity of Adverse Events

Safety and tolerability will be assessed through: * Incidence, severity, and relationship to study treatment of all adverse events (AEs) * Serious adverse events (SAEs) and adverse events leading to treatment discontinuation * Laboratory abnormalities (hematology, clinical chemistry, urinalysis) * Vital signs measurements and physical examination findings * Electrocardiogram (ECG) parameters * All AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Immune-related adverse events (irAEs) will be specifically monitored and managed according to protocol-specified guidelines.

Time frame: At the following predefined visit time points: first dose (baseline), each subsequent cycle treatment day, and the 90-day safety follow-up visit after the last dose.

Health-Related Quality of Life Assessment

Quality of life will be evaluated using validated patient-reported outcome (PRO) instruments: EORTC QLQ-C30: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items FKSI-DRS: Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-Related Symptoms The EORTC QLQ-C30 assesses global health status and quality of life across multiple domains including physical, role, emotional, cognitive, and social functioning. The FKSI-DRS specifically measures disease-related symptoms in renal cell carcinoma patients. Changes from baseline in scale scores will be analyzed.

Time frame: Baseline, every 12 weeks during treatment (up to 17 cycles), at treatment discontinuation, and every 12 weeks during follow-up until disease recurrence (up to 60 months).

A Study of Toripalimab in Adjuvant Therapy After Resection of High-risk Renal Cancer

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes