Clear Cell Renal Cell CarcinomaPhase 2NCT06690697
Combination of Toripalimab and JS004 Therapy for ccRCC
A Phase 2 study testing JS004, Toripalimab and Axitinib in people with Clear Cell Renal Cell Carcinoma, run by Fudan University at 1 site in China.
Trial summary
This study is a single center, prospective, randomized controlled phase II clinical trial aimed at examining the efficacy and safety of the combination of toripalimab and JS004 versus standard therapy for second-line treatment of recurrent and metastatic clear cell renal cell carcinoma patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clear Cell Renal Cell Carcinoma
- What is being tested?
- JS004, Toripalimab and Axitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2024to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient voluntarily participated in this study, signed an informed consent form, and showed good compliance;
- Age ≥ 18 years old;
- Local recurrence or metastatic renal cell carcinoma that has undergone curative surgical resection and has been histologically confirmed;
- 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;
- 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;
- Have at least one measurable lesion (RECIST 1.1);
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- ECOG score 0-1;
- The main organ functions well, and the laboratory examination indicators meet the following criteria:
- 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.
Who cannot join
- Patients with any of the following conditions are not eligible for inclusion in this study:
- Known to have allergic reactions to the therapeutic drugs and/or any excipients used in this study;
- 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;
- Patients who have previously received treatment with anti BTLA or anti HVEM antibodies;
- Subjects with standard second-line treatment and/or contraindications to the use of trastuzumab or JS004;
- Subjects with previous or concurrent malignant tumors (excluding cured cervical cancer, basal or squamous skin cancer);
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- 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;
- Known history of human immunodeficiency virus infection (HIV1/2 antibody positive);
- Female participants who are pregnant, breastfeeding, or planning to become pregnant during the study period;
- Patients with bleeding tendencies (such as active gastrointestinal ulcers) or treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogues;
- 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;
- 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.
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality
Dingwei Ye, MD, +86-021-64175590-2805, dwyeli@163.com
Wenhao Xu, MD, +86 18017312654, xwhao0407@163.com
About this study
Official title: 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 a single center, prospective, randomized controlled phase II clinical trial aimed at examining the efficacy and safety of the combination of toripalimab and JS004 versus standard therapy for second-line treatment of recurrent and metastatic clear cell renal cell carcinoma patients. The study population consists of recurrent and metastatic renal cell carcinoma patients who have undergone radical operation and have been histologically confirmed as clear cell subtype. The subjects will receive JS004 combined with toripalimab or standard second-line treatment. The main endpoint of this study is the Overall Response Rate (ORR). In addition, we will explore the ORR, Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS) of different subgroups of tertiary lymphoid structures (TLSs) presence, location, density, quantity, and maturity in primary tumors. This study is a randomized controlled trial, with a total of 80 participants planned to be included, with regular follow-up for monitoring disease progression and treatment safety. The study will be conducted at Fudan University Cancer Hospital.
- Conditions
- Clear Cell Renal Cell Carcinoma
- Being tested
- JS004, Toripalimab, Axitinib, Sorafenib
- Keywords
- ccRCC, toripalimab, JS004, TLSs, ORR, prognosis
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JS004Drug
200 mg, ivdrip, D1, Q3W, each 21 days as a treatment cycle
ToripalimabDrug
240 mg, ivdrip, D1, Q3W, each 21 days as a treatment cycle
AxitinibDrug
5 mg, po, bid, each 21 days as a treatment cycle
SorafenibDrug
0.4 g, po, bid, each 21 days as a treatment cycle
| Study group | Role | What they receive |
|---|---|---|
| TLS-negative patients with standard second-line treatment (sorafenib or axitinib) | Active comparator | Recurrent or metastatic clear cell renal cell carcinoma patients confirmed to be TLS-negative by HE/IHC assay will be treated with standard second-line treatment (sorafenib or axitinib). Receives: Drug: Axitinib; Drug: Sorafenib |
| TLS-positive patients treated with standard second-line treatment (sorafenib or axitinib) | Active comparator | Recurrent or metastatic clear cell renal cell carcinoma patients confirmed to be TLS- positive by HE/IHC assay will be treated with standard second-line treatment (sorafenib or axitinib). Receives: Drug: Axitinib; Drug: Sorafenib |
| TLS-negative patients treated with toripalimab and JS004 | Experimental | Recurrent or metastatic clear cell renal cell carcinoma patients confirmed to be TLS-negative by HE/IHC assay will be treated with toripalimab and JS004. Receives: Drug: JS004; Drug: Toripalimab |
| TLS-positive patients treated with toripalimab and JS004 | Experimental | Recurrent or metastatic clear cell renal cell carcinoma patients confirmed to be TLS- positive by HE/IHC assay will be treated with toripalimab and JS004. Receives: Drug: JS004; Drug: Toripalimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
The number and proportion of subjects with BOR of CR or PR were calculated, and the Clopper-Pearson method was used to estimate and provide the corresponding 95 % confidence interval.
Measured: 2 years
Secondary outcomes (3)
Disease Control Rate (DCR)
The number and proportion of subjects with BOR of CR, PR or SD were calculated, and the Clopper-Pearson method was used to estimate and provide the corresponding 95 % confidence interval.
Measured: 2 years
Progression Free Survival (PFS)
The PFS rate and its 95 % CI were estimated by Kaplan-Meier method, the median PFS and its 95 % CI were calculated, and the Kaplan-Meier survival curve was drawn.
Measured: 2 years
Overall Survival (OS)
The Kaplan-Meier method was used to estimate the OS rate and its 95 % CI. The median OS and its 95 % CI were calculated, and the Kaplan-Meier survival curve was drawn.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2024
- Study start1 Jun 2024
- Primary completion30 Jun 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clear Cell Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Fudan UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ding-Wei Ye, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06690697
- Sponsor's protocol ID
- 2411091-1
- Status last verified
- Nov 2024
- First submitted
- 14 Nov 2024
- Last updated
- 15 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06690697
- Acronym / sponsor ID
- 2411091-1
- Conditions
- Clear Cell Renal Cell Carcinoma
- Keywords
- ccRCC, toripalimab, JS004, TLSs, ORR, prognosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 15 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a single center, prospective, randomized controlled phase II clinical trial aimed at examining the efficacy and safety of the combination of toripalimab and JS004 versus standard therapy for second-line treatment of recurrent and metastatic clear cell renal cell carcinoma patients. The study population consists of recurrent and metastatic renal cell carcinoma patients who have undergone radical operation and have been histologically confirmed as clear cell subtype. The subjects will receive JS004 combined with toripalimab or standard second-line treatment. The main endpoint of this study is the Overall Response Rate (ORR). In addition, we will explore the ORR, Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS) of different subgroups of tertiary lymphoid structures (TLSs) presence, location, density, quantity, and maturity in primary tumors. This study is a randomized controlled trial, with a total of 80 participants planned to be included, with regular follow-up for monitoring disease progression and treatment safety. The study will be conducted at Fudan University Cancer Hospital.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| TLS-negative patients with standard second-line treatment (sorafenib or axitinib) | Active comparator | Drug: Axitinib, Drug: SorafenibRecurrent or metastatic clear cell renal cell carcinoma patients confirmed to be TLS-negative by HE/IHC assay will be treated with standard second-line treatment (sorafenib or axitinib). |
| TLS-positive patients treated with standard second-line treatment (sorafenib or axitinib) | Active comparator | Drug: Axitinib, Drug: SorafenibRecurrent or metastatic clear cell renal cell carcinoma patients confirmed to be TLS- positive by HE/IHC assay will be treated with standard second-line treatment (sorafenib or axitinib). |
| TLS-negative patients treated with toripalimab and JS004 | Experimental | Drug: JS004, Drug: ToripalimabRecurrent or metastatic clear cell renal cell carcinoma patients confirmed to be TLS-negative by HE/IHC assay will be treated with toripalimab and JS004. |
| TLS-positive patients treated with toripalimab and JS004 | Experimental | Drug: JS004, Drug: ToripalimabRecurrent or metastatic clear cell renal cell carcinoma patients confirmed to be TLS- positive by HE/IHC assay will be treated with toripalimab and JS004. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- The patient voluntarily participated in this study, signed an informed consent form, and showed good compliance;
- Age ≥ 18 years old;
- Local recurrence or metastatic renal cell carcinoma that has undergone curative surgical resection and has been histologically confirmed;
- 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;
- 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;
Key exclusion criteria (13 listed)
- Patients with any of the following conditions are not eligible for inclusion in this study:
- Known to have allergic reactions to the therapeutic drugs and/or any excipients used in this study;
- 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;
- Patients who have previously received treatment with anti BTLA or anti HVEM antibodies;
- Subjects with standard second-line treatment and/or contraindications to the use of trastuzumab or JS004;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JS004200 mg, ivdrip, D1, Q3W, each 21 days as a treatment cycle | Drug | TLS-negative patients treated with toripalimab and JS004, TLS-positive patients treated with toripalimab and JS004 |
| Toripalimab240 mg, ivdrip, D1, Q3W, each 21 days as a treatment cycle | Drug | TLS-negative patients treated with toripalimab and JS004, TLS-positive patients treated with toripalimab and JS004 |
| Axitinib5 mg, po, bid, each 21 days as a treatment cycle | Drug | TLS-negative patients with standard second-line treatment (sorafenib or axitinib), TLS-positive patients treated with standard second-line treatment (sorafenib or axitinib) |
| Sorafenib0.4 g, po, bid, each 21 days as a treatment cycle | Drug | TLS-negative patients with standard second-line treatment (sorafenib or axitinib), TLS-positive patients treated with standard second-line treatment (sorafenib or axitinib) |
Primary outcome
Overall Response Rate (ORR)
Time frame: 2 years
The number and proportion of subjects with BOR of CR or PR were calculated, and the Clopper-Pearson method was used to estimate and provide the corresponding 95 % confidence interval.
3 secondary outcomes
Disease Control Rate (DCR)
Time frame: 2 years
Progression Free Survival (PFS)
Time frame: 2 years
Overall Survival (OS)
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing JS004, Toripalimab and Axitinib in people with Clear Cell Renal Cell Carcinoma, run by Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dingwei Ye, MD (+862164175590, dwyeli@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2024.