Combining Toripalimab and JS004 for treating advanced kidney cancer

A Single Center, Prospective, Randomized Controlled, Second-Line Clinical Study on the Combination of Toripalimab and JS004 in the Treatment for Recurrent and Metastatic Clear Cell Renal Cell Carcinoma

This study is testing if a new combination of two drugs, toripalimab and JS004, can help people with advanced kidney cancer do better than the usual treatment they would receive.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: trastuzumab, radiation, toripalimab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06690697 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial investigates the effectiveness and safety of combining toripalimab and JS004 compared to standard therapy for patients with recurrent and metastatic clear cell renal cell carcinoma (ccRCC). The study will enroll 80 participants who have previously undergone surgery and have confirmed ccRCC. Patients will be randomized to receive either the combination therapy or standard second-line treatment, with the primary focus on measuring the Overall Response Rate (ORR). Additionally, the study will assess other outcomes such as Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS) based on the presence and characteristics of tertiary lymphoid structures (TLSs) in tumor samples.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with recurrent or metastatic clear cell renal cell carcinoma who have previously undergone curative surgery.

Not a fit: Patients who have not received prior systemic therapy or those with non-clear cell renal cell carcinoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could offer a new effective option for patients with advanced kidney cancer who have limited treatment choices.

How similar studies have performed: While this approach is innovative, similar studies combining immunotherapy with targeted therapies have shown promising results in other cancer types.

Eligibility criteria

Inclusion Criteria:

1. The patient voluntarily participated in this study, signed an informed consent form, and showed good compliance;
2. Age ≥ 18 years old;
3. Local recurrence or metastatic renal cell carcinoma that has undergone curative surgical resection and has been histologically confirmed;
4. Previous treatment history of the subject: patients who have received one type of systemic therapy in the past and have progressed or become intolerant, as well as patients who have progressed within 6 months after previous adjuvant or neoadjuvant therapy;
5. Patients are required to provide postoperative tissue wax blocks for research and testing purposes, which should include both renal cancer tissue and normal kidney tissue adjacent to the cancer. Alternatively, at least 20 slices of previous surgical specimens should be provided for HE/IHC/spatial omics testing; The criteria for detecting TLS positivity are: detecting at least one CD3+/CD20+lymphocyte aggregate containing\>700 cells in the tumor;
6. Have at least one measurable lesion (RECIST 1.1);
7. ECOG score 0-1;
8. The main organ functions well, and the laboratory examination indicators meet the following criteria:

(1) Blood routine examination:

* Hemoglobin (HB) ≥ 80g/L;

  ② Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Total white blood cell count ≥ 3.5 × 109/L;

  ③ Platelet count (PLT) ≥ 80 × 109/L; (2) Blood biochemistry test:
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN for liver/bone metastases; ≤ 5 ULN for tumor bone metastases);

  * Serum total bilirubin (TBIL) ≤ 1.5 × ULN; ③ Serum creatinine Cr ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 ml/min; (3) Coagulation function test: Activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time (PT) ≤ 1.5 × ULN; (4) Thyroid function: Thyroid stimulating hormone (TSH) ≤ 1 × ULN (if abnormal, FT3 and FT4 levels should be examined simultaneously. If FT3 and FT4 levels are normal, they can be included in the group) 9. Women of childbearing age must confirm their non pregnancy status before enrollment, and all enrolled subjects (male or female) should take adequate contraceptive measures throughout the entire treatment period and within 4 weeks after the end of treatment; 10. The patient voluntarily joined this study, signed an informed consent form, had good compliance, and was able to accept follow-up from the trial personnel.

Exclusion Criteria:

Patients with any of the following conditions are not eligible for inclusion in this study:

1. Known to have allergic reactions to the therapeutic drugs and/or any excipients used in this study;
2. Four weeks before the first study medication, receive systemic treatment with other anti-tumor drugs (if it has a half-life of five, it can be included in the group), or receive local anti-tumor treatment, or receive clinical investigational drug or device treatment;
3. Patients who have previously received treatment with anti BTLA or anti HVEM antibodies;
4. Subjects with standard second-line treatment and/or contraindications to the use of trastuzumab or JS004;
5. Subjects with previous or concurrent malignant tumors (excluding cured cervical cancer, basal or squamous skin cancer);
6. Active autoimmune diseases that require systemic treatment within the past 3 months, or clinically severe autoimmune disease records, or syndromes that require systemic steroids or immunosuppressants;
7. Known history of human immunodeficiency virus infection (HIV1/2 antibody positive);
8. Female participants who are pregnant, breastfeeding, or planning to become pregnant during the study period;
9. Patients with bleeding tendencies (such as active gastrointestinal ulcers) or treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogues;
10. History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis, symptomatic interstitial lung disease, or any evidence of active pneumonia detected on chest CT scan within 4 weeks prior to the first study drug treatment;
11. According to the researcher's judgment, there are accompanying diseases that pose a serious threat to patient safety or affect the completion of the study.
12. There are other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the study, or interfere with the study results, as well as patients who the researcher deems unsuitable to participate in this study.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Dingwei Ye, MD

Conditions Clear Cell Renal Cell Carcinoma; ccRCC; toripalimab; JS004; TLSs; ORR; prognosis