Advanced RCCPhase 2REMEDY-RCCNCT07611825
Gut Microbiota Modulation for Immunotherapy Resensitization in Advanced Renal Cell Carcinoma
A Phase 2 study testing Toripalimab and Ipilimumab in people with Advanced RCC, run by Jinling Hospital, China at 2 sites in China.
Trial summary
The combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) has significantly improved clinical outcomes in patients with advanced renal cell carcinoma (RCC). However, 40%-60% of patients still develop primary or acquired resistance. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Advanced RCC
- What is being tested?
- Toripalimab and Ipilimumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 2 sitesChina
- Study dates
- 1 Jun 2026to 31 Dec 2028
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathological Diagnosis and Subtype Specification Histologically confirmed metastatic renal cell carcinoma (mRCC) of either clear cell type or non-clear cell type, with non-clear cell histologies restricted to papillary, chromophobe, or unclassified subtypes. Sarcomatoid features are allowed. Other non-clear cell subtypes, including but not limited to collecting duct carcinoma and renal medullary carcinoma, are excluded.
- Based on the pathological subtype, enrolled patients will be assigned to two cohorts: the primary cohort consists of patients with histologically confirmed metastatic clear cell RCC, and the exploratory cohort consists of those with histologically confirmed metastatic non-clear cell RCC (subtypes limited to papillary, chromophobe, or unclassified).
- Immunotherapy Resistance Patients must have received at least two cycles of PD-1/PD-L1 ICI therapy and demonstrated disease progression either during treatment or within six months after the last dose. Progressive disease must be confirmed by the investigator according to RECIST 1.1 criteria, with additional radiographic confirmation performed within four weeks after the initial documented progression.
- Prior Treatment Lines and Sequence Restriction Patients must have received no more than two prior lines of systemic therapy, with no more than one line consisting of a PD-1/PD-L1 ICI. This PD-1/PD-L1 ICI based therapy may have been administered as first-line or second-line treatment for advanced or metastatic RCC, or as neoadjuvant or adjuvant therapy. Furthermore, this line of therapy must be the most recent prior treatment line, meaning that no other anticancer therapy has been administered following its completion.
- Lesion Requirement Patients must have at least one measurable lesion per RECIST v1.1, as assessed by the investigator or by local radiologic evaluation.
- Pre-treatment Tumor Biopsy Quality The pre-treatment tumor biopsy specimen must contain viable tumor tissue accounting for at least 75% of the total examined area.
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- Prior Radiotherapy Washout Participants who have received palliative radiotherapy for non-central nervous system lesions must complete such therapy at least 2 weeks prior to the first dose of study treatment. Participants for whom the only measurable lesions reside within a previously irradiated field are eligible for enrollment, provided that such lesions have shown clear progression and remain accurately measurable.
- Recovery from Prior Treatment Toxicity All toxicities from prior anticancer therapies must have recovered to baseline or to Grade ≤1 according to the CTCAE version 5.0, with the exception of controllable AEs such as hypothyroidism that are clinically insignificant or remain stable under supportive care.
- General Baseline Status Patients must be ≥18 years of age, have an Eastern Cooperative Oncology Group (ECOG) performance status <2, an American Society of Anesthesiologists (ASA) score ≤2, and a life expectancy ≥6 months.
- Adequate Liver Function Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤3 × upper limit of normal (ULN), or ≤5 × ULN in patients with liver metastases. Total bilirubin ≤1.5 × ULN, except for patients with Gilbert's syndrome, in whom bilirubin ≤3.0 mg/dL is allowed.
- Adequate Renal Function Creatinine clearance ≥30 mL/min (Cockcroft-Gault formula) or serum creatinine ≤1.5 × ULN, and urine protein-to-creatinine ratio ≤1 mg/mg.
- Adequate Bone Marrow Function White blood cell count >2.0 × 10⁹/L, absolute neutrophil count >1.5 × 10⁹/L, platelet count >100 × 10⁹/L, lymphocyte count ≥0.3 × 10⁹/L, and hemoglobin ≥90 g/L, with no blood transfusion within 14 days prior to assessment.
- Viral Serology Patients must be negative for human immunodeficiency virus (HIV), negative for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) with negative HBV DNA, and negative for hepatitis C antibody (HCV Ab), or positive with negative HCV RNA.
- Informed Consent Patients must provide written informed consent.
- Compliance Patients must be willing and able to adhere to the study protocol.
Who cannot join
- Recent Microbiota Interference Patients are excluded if they have received systemic antibiotics within 4 weeks prior to screening, or have received any live bacterial preparations or commercial prebiotics within 2 weeks prior to screening, or are currently using or plan to use probiotics, yogurt, or foods supplemented with bacteria during the treatment period.
- Immune-Related Severe Toxicity or Autoimmune Status
- Patients are excluded if they meet any of the following criteria:
- Have a history of permanent discontinuation of immunotherapy due to immune-mediated adverse events;
- Have active or known autoimmune disease, except for type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, and vitiligo;
- Have an immunosuppressive status, defined as confirmed immunodeficiency, receipt of systemic corticosteroids at a dose equivalent to >10 mg of prednisone per day or other immunosuppressive agents (excluding inhaled or topical corticosteroids), or a history of active autoimmune disease requiring systemic therapy within the past 2 years.
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- Prior Specific Immunotherapy or Excessive Therapy Patients are excluded if they have received prior treatment with a CTLA-4 ICI or more than two prior systemic therapy regimens.
- Gastrointestinal Risk Factors Patients are excluded if they have a history of inflammatory bowel disease (including Crohn's disease or ulcerative colitis); chronic severe diarrhea; or grade ≥3 immune-related colitis; or present with gastrointestinal metastatic lesions; or have undergone major abdominal surgery that may impair intestinal absorption or peristaltic function.
- Oral Administration Barrier Patients are excluded if they have dysphagia or are unable to take the required oral study medication.
- Rapid Tumor Progression Patients are excluded if they have rapidly progressive disease such that, in the opinion of the investigator, they cannot safely tolerate a 4-week washout period and a 2-week reconditioning period.
- Active Interstitial Lung Disease or Pneumonitis Patients with active interstitial lung disease or pneumonitis, or a history of either condition requiring systemic steroid therapy, are excluded.
- Uncontrolled Brain Metastases or Central Nervous System Disease Patients with known brain metastases, cranial epidural disease, or significant vasogenic edema are excluded unless they have received adequate radiotherapy or surgery and have been stable for at least 4 weeks prior to the first dose of study treatment.
- Severe Cardiac Disease Patients are excluded if they have a history of myocarditis or congestive heart failure (New York Heart Association [NYHA] class III-IV), unstable angina, uncontrolled severe arrhythmia, or myocardial infarction within 6 months prior to enrollment.
- Recent Other Antineoplastic Treatment Patients are excluded if they have received, prior to the first dose of study treatment:any small molecule kinase inhibitor within 2 weeks; cytotoxic agents, biologics, or other systemic anticancer therapies within 4 weeks; radiotherapy for bone metastases within 2 weeks, or any other radiotherapy within 4 weeks.
- Planned Other Antineoplastic Treatment Patients are excluded if they require any other systemic or local antineoplastic therapy during the study period, with the exception of bisphosphonates or denosumab for the management of bone metastases.
- Active Second Malignancy Patients are excluded if they have a second active malignancy diagnosed within the preceding 2 years, with the exception of indolent or early-stage tumors, including non-melanoma skin cancer and carcinoma in situ.
- Laboratory Abnormalities
- Patients are excluded if they meet any of the following criteria:
- White blood cell count <2.0 × 10⁹/L, absolute neutrophil count <1.5 × 10⁹/L, or platelet count <100 × 10⁹/L;
- AST/ALT >3 × ULN, or >5 × ULN in patients with liver metastases, or total bilirubin >1.5 × ULN (except for Gilbert's syndrome); ③Creatinine clearance <30 mL/min or serum creatinine >1.5 × ULN.
- Other Uncontrolled Comorbidities
- Patients are excluded if they have any of the following:
- Uncontrolled tumor-related pain, with painful lesions requiring palliative radiotherapy to be managed prior to enrollment;
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage more frequently than once per month, the presence of an indwelling catheter such as a PleurX® device is permitted; ③Moderate to severe hepatic impairment, defined as Child-Pugh class B or C; ④Uncontrolled or symptomatic hypercalcemia.
- Other General Exclusions
- Patients are excluded if they meet any of the following criteria:
- Have received prior allogeneic stem cell transplantation or solid organ transplantation;
- Have active hepatitis B (HBV DNA positive), active hepatitis C (HCV RNA positive), or HIV infection;
- Have undergone major surgery within 4 weeks prior to study treatment;
- Have a history of allergy to food or antibiotics; ⑤Are pregnant, breastfeeding, or plan to conceive or father children during the study period (from pre-screening or screening visit until 120 days after the last dose); ⑥Require dialysis, have malabsorption syndrome, uncontrolled electrolyte disturbances, or require specific anticoagulants such as warfarin; ⑦Have any medical or psychological condition that may compromise safety or compliance.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Not yet recruiting
Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University
Nanjing, Jiangsu, 210000
Le Qu, Ph.D., +86 15720625952, septsoul@hotmail.com
Shaochuan Chen, chensc4556@163.com
- Recruiting
Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University
Nanjing, Jiangsu, 210002
le Qu, P.D, 15720625951, septsoul@hotmail.com
About this study
Official title: REMEDY-RCC: Gut Microbiota Modulation for Immunotherapy Resensitization in Advanced Renal Cell Carcinoma - A Prospective, Exploratory, Single-Center Study
The combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) has significantly improved clinical outcomes in patients with advanced renal cell carcinoma (RCC). However, 40%-60% of patients still develop primary or acquired resistance. For those with resistant disease, current immune rechallenge strategies have yet to demonstrate clear clinical benefit. Emerging evidence indicates that the gut microbiota plays a critical role in modulating responses to immunotherapy. Microbiota-modulating approaches, including fecal microbiota transplantation (FMT) and live bacterial formulations such as CBM588, have shown preliminary potential to enhance sensitivity to immunotherapy and improve patient outcomes. Nevertheless, whether gut microbiota modulation can resensitize advanced RCC to immunotherapy remains to be investigated.
The REMEDY-RCC trial is an investigator-initiated, prospective, open-label, phase II, parallel two-cohort exploratory study primarily designed to investigate whether gut microbiota modulation can restore sensitivity to immunotherapy in patients with advanced RCC. Given the substantial differences in the tumor immune microenvironment and response to ICIs between clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC), this study employs a parallel two-cohort design to stratify these two patient populations: a primary cohort consisting of patients with metastatic ccRCC, and an exploratory cohort consisting of patients with metastatic nccRCC. The primary and secondary endpoints will be analyzed in the primary cohort, whereas the exploratory cohort will be used solely for exploratory and descriptive analyses. The study plans to enroll approximately 33 adult patients with advanced or metastatic RCC, including 27 with metastatic ccRCC and 6 with metastatic nccRCC. Eligible patients will receive the following sequential interventions: bowel decontamination with amoxicillin-clavulanate potassium followed by polyethylene glycol (PEG) solution, high-dose gut colonization and maintenance supplementation with live Clostridium butyricum powder combined with soluble dietary fiber, and immune rechallenge therapy consisting of a PD-1 immune checkpoint inhibitor (ICI) combined with four cycles of a CTLA-4 ICI, followed by maintenance therapy with the PD-1 ICI alone. Treatment will continue until disease progression, unacceptable toxicity, completion of the planned treatment cycles, or withdrawal of consent.
Read more
The REMEDY-RCC trial requires specific follow-up for enrolled patients. Radiological response is assessed longitudinally using computed tomography (CT). Tissue and body fluid samples collected from patients will be used for biomarker and multi-omic analyses.
The primary endpoint of the trial is the objective response rate (ORR) in the primary cohort, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Sample size for the primary cohort was determined using Simon's optimal two-stage design, with a one-sided α of 0.10 and power (1-β) of 0.80. The unacceptable response rate (P0) was set at 17.4%, based on the ORR observed in the FRACTION-RCC study for nivolumab plus ipilimumab rechallenge in patients with metastatic ccRCC who had progressed after prior immunotherapy. The target response rate (P1) was established considering that FMT has been shown to increase ORR by approximately 20% in immunotherapy-resistant melanoma. Given that metastatic RCC and melanoma are both considered immunologically responsive tumor types, a comparable therapeutic benefit from gut microbiota remodeling is anticipated. Accordingly, P1 was set at 37.4%. This effect size is clinically meaningful and would be non-inferior to the clinical efficacy of cabozantinib in metastatic RCC that has progressed following immunotherapy.
The primary cohort will initially enroll six patients for safety assessment. If the treatment is deemed safe, further accrual will follow Simon's two-stage design, and enrollment of the exploratory cohort will be considered. After these six patients, an additional six patients will be enrolled, bringing the total to 12, at which point an interim analysis will be performed. If the number of objective responses at the interim analysis is ≤ 2, the trial will be terminated early. If ≥3 objective responses are observed, an additional 12 patients will be enrolled, resulting in a total sample size of 24 patients. Accounting for a potential 10% dropout rate, the study plans to enroll 27 patients in total.
The exploratory cohort is planned to enroll no more than 6 patients (not exceeding 20% of the total enrollment), with a fixed-sample descriptive design. The sample size calculation is not based on statistical hypothesis testing, and all efficacy endpoints will be reported using descriptive statistics. The total planned sample size is 33 patients, comprising 27 patients in the primary cohort and 6 patients in the exploratory cohort.
- Conditions
- Advanced RCC
- Being tested
- Toripalimab, Ipilimumab
- Keywords
- Gut Microbiota Modulation, Advanced Renal Cell Carcinoma, Immunotherapy, Resensitization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Also called anti-PD-1 monoclonal antibody
Beginning on day 15, patients receive toripalimab (240 mg, Q3W IV) until disease progression, unacceptable toxicity, completion of the prespecified treatment course, or withdrawal from the study. Dose modifications are as follows: administration of toripalimab may be delayed in patients suspected of experiencing grade 3 or higher adverse events attributable to toripalimab, as per CTCAE version 5.0. In the event of serious adverse reactions, treatment discontinuation is permitted. Investigators may adjust the dosing regimen for patients achieving a complete or partial response, in accordance with the study protocol.
IpilimumabDrug
Also called anti-CTLA-4 monoclonal antibody
Patients will receive four cycles of ipilimumab (1mg/kg, Q3W IV). During study treatment, if a patient experiences Grade ≥2 or intolerable adverse events, the investigator may evaluate the patient's condition and resume toripalimab plus ipilimumab therapy after the toxicity has resolved to Grade ≤1 or returned to baseline, with a treatment interruption not exceeding 21 days in principle. Ipilimumab should be discontinued, and the patient should enter the study follow-up phase, if any of the following criteria are met:①Grade ≥3 immune-related adverse events,② symptomatic progression leading both the physician and patient to opt for an alternative treatment, ③patient refusal to continue ipilimumab therapy, or the investigator's judgment that ipilimumab is no longer appropriate for the patient.
| Study group | Role | What they receive |
|---|---|---|
| Gut Microbiota Modulation Combined with Dual Immunotherapy | Experimental | Eligible patients first received oral amoxicillin-clavulanate potassium (914mg, BID) for 5 days, followed by a 1-day washout. On day 7, PEG solution (74g, single dose PO) was administered for intestinal decontamination. From day 8 onward, a high-dose regimen of live Clostridium butyricum powder (120mg, BID PO) combined with soluble dietary fiber (5g, BID PO) was given orally for seven days to promote gut colonization. Beginning on day 15, patients received four cycles of toripalimab (240 mg, Q3W) plus ipilimumab (1mg/kg, Q3W) intravenously. During this combination immunotherapy period, subjects continued to take oral live Clostridium butyricum powder (80mg, BID PO) and soluble dietary fiber (10g, BID PO) until the initiation of the fifth immunotherapy cycle. From the fifth cycle onward, patients switched to toripalimab monotherapy (240mg, Q3W) until disease progression, unacceptable toxicity, completion of the prespecified treatment course, or withdrawal from the study. Receives: Drug: Toripalimab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate(ORR)
The efficacy population (EP) comprised patients who received at least one dose of toripalimab plus ipilimumab and had measurable disease at baseline. Tumor responses were assessed by an independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The best overall response was defined as either complete response (CR) or partial response (PR). The primary endpoint was the proportion of patients in the EP achieving CR or PR. All responses required confirmation by repeat imaging performed at least four weeks after the initial documentation.
Measured: Up to 2 years after treatment
Secondary outcomes (9)
Progression-Free Survival（PFS）
PFS was defined as the time from the first treatment date to the first documented disease progression per RECIST version 1.1 as assessed by an IRC, or death from any cause, whichever occurred first. For patients who had not experienced an event by the analysis data cutoff date, data were censored at the date of the last radiological evaluation.
Measured: Up to 2 years after treatment
Disease Control Rate（DCR）
Per RECIST version 1.1, the proportion of patients in the EP with a best overall response of CR, PR, or stable disease (SD) was assessed by an IRC. Confirmed responses (CR/PR) required repeat imaging at least 4 weeks after the initial documentation. SD had to be maintained for at least 8 weeks from the first assessment.
Measured: Up to 2 years after treatment
Duration of Response（DoR）
Among patients achieving a CR or PR, the DOR was defined as the time from the first documented response (CR or PR) to the first documented disease progression per RECIST v1.1 or death from any cause, whichever occurred first.
Measured: Up to 2 years after treatment
Overall Survival（OS）
OS was defined as the time from the first treatment date to death from any cause. Patients who were still alive or lost to follow-up at the analysis data cutoff date were censored at the date of the last known alive status.
Measured: Up to 2 years after treatment
Safety and Tolerability
Safety and tolerability were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. The safety analysis set (SAS) comprised all patients who received at least one dose of toripalimab plus ipilimumab. Evaluated parameters included the incidence, severity, and causal relationship to the treatment regimen of treatment-related adverse events (AEs), serious adverse events (SAEs), and immune-related adverse events (irAEs), as well as the proportion of patients with treatment discontinuation, dose delay, or dose adjustment due to adverse events.
Measured: Up to 2 years after treatment
Patient quality of life - Assessment will be performed using the NCCN FKSI-19+.
The NCCN FKSI-19⁺ is a disease-specific symptom burden scale for patients with renal cell carcinoma. It comprises 19 core items that capture disease-related symptoms, treatment side effects, and functional status, making it suitable for longitudinal clinical monitoring and efficacy evaluation. The assessment time points include: baseline (before treatment), week 6 (with an allowable window of ±7 days), week 12 (with an allowable window of ±7 days), and every 12 weeks thereafter (±7 days) until the end of treatment.
Measured: Up to 2 years after treatment
Patient quality of life - Assessment will be performed using the QLQ-C30.
The EORTC QLQ-C30 is a core quality of life questionnaire developed by the European Organisation for Research and Treatment of Cancer. It comprises 30 items that assess five functional domains (physical, role, cognitive, emotional, and social), three symptom domains (fatigue, nausea/vomiting, and pain), global health status, and several single-item symptom measures. It is widely used for the standardized assessment of health-related quality of life in patients with malignant tumors. The assessment time points include: baseline (before treatment), week 6 (with an allowable window of ±7 days), week 12 (with an allowable window of ±7 days), and every 12 weeks thereafter (±7 days) until the end of treatment.
Measured: Up to 2 years after treatment
Patient quality of life - Assessment will be performed using the EuroQoL EQ-5D-5L.
The EuroQoL EQ-5D-5L is a preference-based generic health status instrument consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with five severity levels, along with a visual analog scale. It is used to derive health utility values and is applicable for cost-utility analysis and population health surveys. The assessment time points include: baseline (before treatment), week 6 (with an allowable window of ±7 days), week 12 (with an allowable window of ±7 days), and every 12 weeks thereafter (±7 days) until the end of treatment.
Measured: Up to 2 years after treatment
Patient quality of life - Assessment will be performed using the HADS.
The Hospital Anxiety and Depression Scale (HADS) comprises 14 items, with seven items each for the anxiety and depression subscales, scored on a four-point scale from 0 to 3. It was designed for use in non-psychiatric hospitalized patients to minimize the interference of somatic symptoms with the assessment of emotional states. The scale demonstrates good clinical feasibility, reliability, and validity. The assessment time points include: baseline (before treatment), week 6 (with an allowable window of ±7 days), week 12 (with an allowable window of ±7 days), and every 12 weeks thereafter (±7 days) until the end of treatment.
Measured: Up to 2 years after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2026
- Study start1 Jun 2026
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced RCCStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- An Investigator-initiated, Prospective, Open-label, Phase II, Parallel Two-cohort Exploratory Trial
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jinling Hospital, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Le Qu, Jinling Hospital, China
- Investigators
- Le Qu, Ph.D., Principal investigator, Jinling Hospital, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07611825
- Sponsor's protocol ID
- 2026DZKY-087-01
- Acronym
- REMEDY-RCC
- Status last verified
- Jul 2026
- First submitted
- 11 May 2026
- Last updated
- 3 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REMEDY-RCC: Gut Microbiota Modulation for Immunotherapy Resensitization in Advanced Renal Cell Carcinoma - A Prospective, Exploratory, Single-Center Study
- ClinicalTrials.gov ID
- NCT07611825
- Acronym / sponsor ID
- REMEDY-RCC / 2026DZKY-087-01
- Conditions
- Advanced RCC
- Keywords
- Gut Microbiota Modulation, Advanced Renal Cell Carcinoma, Immunotherapy, Resensitization
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- Jinling Hospital, ChinaUniversity, hospital or other
- Study start
- 1 Jun 2026 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 28 May 2026 (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.
The combination of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) has significantly improved clinical outcomes in patients with advanced renal cell carcinoma (RCC). However, 40%-60% of patients still develop primary or acquired resistance. For those with resistant disease, current immune rechallenge strategies have yet to demonstrate clear clinical benefit. Emerging evidence indicates that the gut microbiota plays a critical role in modulating responses to immunotherapy. Microbiota-modulating approaches, including fecal microbiota transplantation (FMT) and live bacterial formulations such as CBM588, have shown preliminary potential to enhance sensitivity to immunotherapy and improve patient outcomes. Nevertheless, whether gut microbiota modulation can resensitize advanced RCC to immunotherapy remains to be investigated.
The REMEDY-RCC trial is an investigator-initiated, prospective, open-label, phase II, parallel two-cohort exploratory study primarily designed to investigate whether gut microbiota modulation can restore sensitivity to immunotherapy in patients with advanced RCC. Given the substantial differences in the tumor immune microenvironment and response to ICIs between clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC), this study employs a parallel two-cohort design to stratify these two patient populations: a primary cohort consisting of patients with metastatic ccRCC, and an exploratory cohort consisting of patients with metastatic nccRCC. The primary and secondary endpoints will be analyzed in the primary cohort, whereas the exploratory cohort will be used solely for exploratory and descriptive analyses. The study plans to enroll approximately 33 adult patients with advanced or metastatic RCC, including 27 with metastatic ccRCC and 6 with metastatic nccRCC. Eligible patients will receive the following sequential interventions: bowel decontamination with amoxicillin-clavulanate potassium followed by polyethylene glycol (PEG) solution, high-dose gut colonization and maintenance supplementation with live Clostridium butyricum powder combined with soluble dietary fiber, and immune rechallenge therapy consisting of a PD-1 immune checkpoint inhibitor (ICI) combined with four cycles of a CTLA-4 ICI, followed by maintenance therapy with the PD-1 ICI alone. Treatment will continue until disease progression, unacceptable toxicity, completion of the planned treatment cycles, or withdrawal of consent.
The REMEDY-RCC trial requires specific follow-up for enrolled patients. Radiological response is assessed longitudinally using computed tomography (CT). Tissue and body fluid samples collected from patients will be used for biomarker and multi-omic analyses.
The primary endpoint of the trial is the objective response rate (ORR) in the primary cohort, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Sample size for the primary cohort was determined using Simon's optimal two-stage design, with a one-sided α of 0.10 and power (1-β) of 0.80. The unacceptable response rate (P0) was set at 17.4%, based on the ORR observed in the FRACTION-RCC study for nivolumab plus ipilimumab rechallenge in patients with metastatic ccRCC who had progressed after prior immunotherapy. The target response rate (P1) was established considering that FMT has been shown to increase ORR by approximately 20% in immunotherapy-resistant melanoma. Given that metastatic RCC and melanoma are both considered immunologically responsive tumor types, a comparable therapeutic benefit from gut microbiota remodeling is anticipated. Accordingly, P1 was set at 37.4%. This effect size is clinically meaningful and would be non-inferior to the clinical efficacy of cabozantinib in metastatic RCC that has progressed following immunotherapy.
The primary cohort will initially enroll six patients for safety assessment. If the treatment is deemed safe, further accrual will follow Simon's two-stage design, and enrollment of the exploratory cohort will be considered. After these six patients, an additional six patients will be enrolled, bringing the total to 12, at which point an interim analysis will be performed. If the number of objective responses at the interim analysis is ≤ 2, the trial will be terminated early. If ≥3 objective responses are observed, an additional 12 patients will be enrolled, resulting in a total sample size of 24 patients. Accounting for a potential 10% dropout rate, the study plans to enroll 27 patients in total.
The exploratory cohort is planned to enroll no more than 6 patients (not exceeding 20% of the total enrollment), with a fixed-sample descriptive design. The sample size calculation is not based on statistical hypothesis testing, and all efficacy endpoints will be reported using descriptive statistics. The total planned sample size is 33 patients, comprising 27 patients in the primary cohort and 6 patients in the exploratory cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- An Investigator-initiated, Prospective, Open-label, Phase II, Parallel Two-cohort Exploratory Trial
| Arm | Type | Receives |
|---|---|---|
| Gut Microbiota Modulation Combined with Dual Immunotherapy | Experimental | Drug: Toripalimab, Drug: IpilimumabEligible patients first received oral amoxicillin-clavulanate potassium (914mg, BID) for 5 days, followed by a 1-day washout. On day 7, PEG solution (74g, single dose PO) was administered for intestinal decontamination. From day 8 onward, a high-dose regimen of live Clostridium butyricum powder (120mg, BID PO) combined with soluble dietary fiber (5g, BID PO) was given orally for seven days to promote gut colonization. Beginning on day 15, patients received four cycles of toripalimab (240 mg, Q3W) plus ipilimumab (1mg/kg, Q3W) intravenously. During this combination immunotherapy period, subjects continued to take oral live Clostridium butyricum powder (80mg, BID PO) and soluble dietary fiber (10g, BID PO) until the initiation of the fifth immunotherapy cycle. From the fifth cycle onward, patients switched to toripalimab monotherapy (240mg, Q3W) until disease progression, unacceptable toxicity, completion of the prespecified treatment course, or withdrawal from the study. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Pathological Diagnosis and Subtype Specification Histologically confirmed metastatic renal cell carcinoma (mRCC) of either clear cell type or non-clear cell type, with non-clear cell histologies restricted to papillary, chromophobe, or unclassified subtypes. Sarcomatoid features are allowed. Other non-clear cell subtypes, including but not limited to collecting duct carcinoma and renal medullary carcinoma, are excluded.
- Based on the pathological subtype, enrolled patients will be assigned to two cohorts: the primary cohort consists of patients with histologically confirmed metastatic clear cell RCC, and the exploratory cohort consists of those with histologically confirmed metastatic non-clear cell RCC (subtypes limited to papillary, chromophobe, or unclassified).
- Immunotherapy Resistance Patients must have received at least two cycles of PD-1/PD-L1 ICI therapy and demonstrated disease progression either during treatment or within six months after the last dose. Progressive disease must be confirmed by the investigator according to RECIST 1.1 criteria, with additional radiographic confirmation performed within four weeks after the initial documented progression.
- Prior Treatment Lines and Sequence Restriction Patients must have received no more than two prior lines of systemic therapy, with no more than one line consisting of a PD-1/PD-L1 ICI. This PD-1/PD-L1 ICI based therapy may have been administered as first-line or second-line treatment for advanced or metastatic RCC, or as neoadjuvant or adjuvant therapy. Furthermore, this line of therapy must be the most recent prior treatment line, meaning that no other anticancer therapy has been administered following its completion.
- Lesion Requirement Patients must have at least one measurable lesion per RECIST v1.1, as assessed by the investigator or by local radiologic evaluation.
Key exclusion criteria (30 listed)
- Recent Microbiota Interference Patients are excluded if they have received systemic antibiotics within 4 weeks prior to screening, or have received any live bacterial preparations or commercial prebiotics within 2 weeks prior to screening, or are currently using or plan to use probiotics, yogurt, or foods supplemented with bacteria during the treatment period.
- Immune-Related Severe Toxicity or Autoimmune Status
- Have a history of permanent discontinuation of immunotherapy due to immune-mediated adverse events;
- White blood cell count <2.0 × 10⁹/L, absolute neutrophil count <1.5 × 10⁹/L, or platelet count <100 × 10⁹/L;
- Uncontrolled tumor-related pain, with painful lesions requiring palliative radiotherapy to be managed prior to enrollment;
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 |
|---|---|---|
| ToripalimabAlso: anti-PD-1 monoclonal antibodyBeginning on day 15, patients receive toripalimab (240 mg, Q3W IV) until disease progression, unacceptable toxicity, completion of the prespecified treatment course, or withdrawal from the study. Dose modifications are as follows: administration of toripalimab may be delayed in patients suspected of experiencing grade 3 or higher adverse events attributable to toripalimab, as per CTCAE version 5.0. In the event of serious adverse reactions, treatment discontinuation is permitted. Investigators may adjust the dosing regimen for patients achieving a complete or partial response, in accordance with the study protocol. | Drug | Gut Microbiota Modulation Combined with Dual Immunotherapy |
| IpilimumabAlso: anti-CTLA-4 monoclonal antibodyPatients will receive four cycles of ipilimumab (1mg/kg, Q3W IV). During study treatment, if a patient experiences Grade ≥2 or intolerable adverse events, the investigator may evaluate the patient's condition and resume toripalimab plus ipilimumab therapy after the toxicity has resolved to Grade ≤1 or returned to baseline, with a treatment interruption not exceeding 21 days in principle. Ipilimumab should be discontinued, and the patient should enter the study follow-up phase, if any of the following criteria are met:①Grade ≥3 immune-related adverse events,② symptomatic progression leading both the physician and patient to opt for an alternative treatment, ③patient refusal to continue ipilimumab therapy, or the investigator's judgment that ipilimumab is no longer appropriate for the patient. | Drug | Gut Microbiota Modulation Combined with Dual Immunotherapy |
Primary outcome
Objective Response Rate(ORR)
Time frame: Up to 2 years after treatment
The efficacy population (EP) comprised patients who received at least one dose of toripalimab plus ipilimumab and had measurable disease at baseline. Tumor responses were assessed by an independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The best overall response was defined as either complete response (CR) or partial response (PR). The primary endpoint was the proportion of patients in the EP achieving CR or PR. All responses required confirmation by repeat imaging performed at least four weeks after the initial documentation.
9 secondary outcomes
Progression-Free Survival（PFS）
Time frame: Up to 2 years after treatment
Disease Control Rate（DCR）
Time frame: Up to 2 years after treatment
Duration of Response（DoR）
Time frame: Up to 2 years after treatment
Overall Survival（OS）
Time frame: Up to 2 years after treatment
Safety and Tolerability
Time frame: Up to 2 years after treatment
Patient quality of life - Assessment will be performed using the NCCN FKSI-19+.
Time frame: Up to 2 years after treatment
Patient quality of life - Assessment will be performed using the QLQ-C30.
Time frame: Up to 2 years after treatment
Patient quality of life - Assessment will be performed using the EuroQoL EQ-5D-5L.
Time frame: Up to 2 years after treatment
Patient quality of life - Assessment will be performed using the HADS.
Time frame: Up to 2 years after treatment
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 3 Aug 2026.
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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.
Le Qu, Ph.D. principal investigator
Jinling Hospital, China
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Toripalimab and Ipilimumab in people with Advanced RCC, run by Jinling Hospital, China at 2 sites 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 15 inclusion and 30 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 3 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 Le Qu, Ph.D. (+86 15720625951, septsoul@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate(ORR) (time frame: Up to 2 years after treatment). 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 3 Aug 2026.