Renal Cell CarcinomaPhase 2NESCIONCT05148546
Neoadjuvant Study With Combination Immuno-oncology for Primary Clear Cell Renal Cell Cancer
A Phase 2 study testing Neoadjuvant nivolumab, Neoadjuvant ipilimumab and Neoadjuvant relatlimab in people with Renal Cell Carcinoma, run by The Netherlands Cancer Institute at 2 sites in 2 countries.
Trial summary
The NESCIO-trial is a multicenter, randomized, open-label, three-arm phase II trial investigating different combinations of neoadjuvant immunotherapy in patients with primary, resectable, intermediate to high-risk, clear-cell renal cell carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Neoadjuvant nivolumab, Neoadjuvant ipilimumab and Neoadjuvant relatlimab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 28 Apr 2022to Apr 2029
- 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
- Adults at least 18 years of age;
- World Health Organization (WHO) Performance Status 0 or 1;
- Histologically confirmed resectable clear cell RCC (measurable according to RECIST 1.1), that can be biopsied, and no history of distant metastases;
- Intermediate to high risk will be based on clinical TNM and biopsy nuclear grade. These are:
- cT1b-cT2a grade 4 cN0 cM0
- cT2b grade 3 cN0 cM0
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- cT3 any grade cN0 cM0
- cT4 any grade cN0 cM0
- cT any cN1 (fully resectable) cM0
- No other malignancies, except adequately treated and a cancer-related life-expectancy of more than 5 years;
- Patient willing to undergo triple tumor biopsies and extra blood withdrawal during screening and in case of relapse;
- No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1, or LAG-3;
- No immunosuppressive medications within 2 weeks prior start immunotherapy;
- Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.5x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, Creatinine ≤1.5x ULN, AST ≤ 1.5 x ULN, ALT ≤ 1.5 x ULN, Bilirubin ≤1.5 X ULN, normal CK and Troponin T, normal LDH;
- Women of childbearing potential must use appropriate method(s) of contraception. They should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug;
- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment;
- Women who are not of childbearing potential (i.e., who are postmenopausal), or surgically sterile as well as azoospermic men do not require contraception;
- Patient is capable of understanding and complying with the protocol requirements and has signed the Informed Consent document.
Who cannot join
- Distantly metastasized RCC;
- Brain metastases (based on symptoms);
- Non-clear cell RCC;
- No measurable lesion according to RECIST 1.1;
- Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy;
- Prior CTLA-4 or PD-1/PD-L1 or LAG-3 targeting immunotherapy;
Show all 19Show fewer
- Radiotherapy prior or post-surgery;
- Patients will be excluded if they test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody), indicating acute or chronic infection; if treated and being at least one year free from HCV patients are allowed to participate;
- Patients will be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
- Allergies and Adverse Drug Reactions (like mastocytosis);
- History of severe hypersensitivity reaction to any monoclonal antibody;
- Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug(s) hazardous or obscure the interpretation of toxicity or adverse events;
- Pregnant or nursing;
- Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids;
- Use of other investigational drugs before study drug administration 30 days and 5 half-times before study inclusion.
- Relatlimab-specific exclusion Criteria:
- Participants with history of myocarditis, regardless of etiology;
- Troponin T (TnT) > 2 × institutional ULN. Participants with TnT levels between > 1 to 2 × ULN will be permitted if a repeat levels within 24 hours are ≤ 1 ULN. If TnT levels are between >1 to 2 × ULN within 24 hours, the participant may undergo a cardiac consultation and be considered for treatment, following cardiologist recommendation. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT repeat levels beyond 24 hours are < 2 × ULN, the participant may undergo a cardiac consultation and be considered for treatment, following cardiologist recommendation. Notification of the decision to enroll the participant following cardiologist recommendation has to be made to the BMS Medical Monitor or designee.
- Left ventricular ejection fraction (LVEF) assessment with documented LVEF < 50% by either transthoracic echocardiogram (TTE) or multigated acquisition (MUGA) scan (TTE preferred test) within 6 months prior to start of study treatment.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Netherlands1 site
Netherlands Cancer Institute
Amsterdam, North Holland, 1066CX
United Kingdom1 site
Royal Free London NHS Foundation Trust
London, NW3 2QG
About this study
Official title: Prospective, Randomized, Neoadjuvant Phase II Study With Combination Immuno-oncology in Primary Clear Cell Renal Cancer at Risk for Recurrence or Distant Metastases (NESCIO-trial)
The NESCIO-trial is a multicenter, randomized, open-label, three-arm phase II trial investigating different combinations of neoadjuvant immunotherapy in patients with primary, resectable, intermediate to high-risk, clear-cell renal cell carcinoma. In this trial patients will be randomized 1:1:1 to receive either 2 cycles of nivolumab 360mg every 3 weeks (arm A), 2 cycles of ipilimumab 1 mg/kg + nivolumab 3 mg/kg every 3 weeks (arm B) or 2 cycles of relatlimab 360mg + nivolumab 360mg every 3 weeks (arm C), prior to surgery at week 7.
After 42 patients (14 per arm) have been recruited, an interim analysis will be performed to evaluate the observed efficacy and toxicity within each arm and either allow for early discontinuation of the treatment or continuing recruitment for the second stage. As the primary endpoint, the pathological response (decrease in tumor) will be evaluated. If at most one pathologic response in the primary tumor is observed, the treatment arm will be closed for insufficient activity on the primary tumor. If at least 2 pathologic responses are observed, 9 additional patients will be included to a total of 23 patients per cohort. A maximum of 69 patients will be recruited for this study.
Follow up will start at week 12 with a CT-scan according to the national/center's standard. Patients will be evaluated every 3 months by physical examination and lab testing for up to two years, thereafter according to institutional guidelines up to 5 years following surgery.
- Conditions
- Renal Cell Carcinoma
- Being tested
- Neoadjuvant nivolumab, Neoadjuvant ipilimumab, Neoadjuvant relatlimab
- Keywords
- Resectable renal cell carcinoma, Checkpoint inhibition, Immunotherapy, PD-1 inhibitor, CTLA-4 inhibitor, LAG-3 inhibitor, Nivolumab, Ipilimumab, Relatlimab, Neoadjuvant, NESCIO, M21NSC, Checkpoint blockade
- 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.
Neoadjuvant nivolumabDrug
Also called Opdivo
Patients will receive 2 cycles of nivolumab 360mg (arm A and C) or 3mg/kg (arm B) every 3 weeks followed by a nephrectomy.
Neoadjuvant ipilimumabDrug
Also called Yervoy
Patients will receive 2 cycles of ipilimumab 1mg/kg every 3 weeks followed by a nephrectomy.
Neoadjuvant relatlimabDrug
Patients will receive 2 cycles of relatlimab 360mg every 3 weeks followed by a nephrectomy.
| Study group | Role | What they receive |
|---|---|---|
| A: Neoadjuvant nivolumab | Experimental | Neoadjuvant 2 cycles of nivolumab 360mg every 3 weeks Receives: Drug: Neoadjuvant nivolumab |
| B: Neoadjuvant nivolumab + ipilimumab | Experimental | Neoadjuvant 2 cycles of nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks Receives: Drug: Neoadjuvant nivolumab; Drug: Neoadjuvant ipilimumab |
| C: Neoadjuvant nivolumab + relatlimab | Experimental | Neoadjuvant 2 cycles of nivolumab 360mg + relatlimab 360mg every 3 weeks Receives: Drug: Neoadjuvant nivolumab; Drug: Neoadjuvant relatlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic response rate
Pathologic response rate is defined as the proportion of patients demonstrating a complete pathologic or partial pathologic response, according to central revision (pathology of NKI)
Measured: At 6 weeks
Secondary outcomes (10)
Safety, measured by the frequency of immune-related adverse events leading to postponing of surgery for >2 weeks
Measured: At 8 weeks
Objective response rate
ORR is defined as the proportion of patients demonstrating a complete or partial response according to RECIST 1.1
Measured: At 6 weeks
Recurrence Free Survival (RFS)
RFS is defined as the time from randomization to recurrence or death from any cause, whichever occurs first. Subjects last known to be alive, who have not experience recurrence, will be censored.
Measured: Up to 5 years after start of treatment
Event-free Survival (EFS)
EFS is defined as the time from randomization to recurrence, distant metastasis, or death from any cause, whichever occurs first. Subjects who are event-free at the end of follow-up will be censored.
Measured: Up to 5 years after start of treatment
Rate of distant metastases
The proportion of patients starting treatment who experience distant metastases during follow-up.
Measured: Up to 5 years after start of treatment
Rate of local recurrences
The proportion of patients starting treatment who experience a local recurrence during follow-up.
Measured: Up to 5 years after start of treatment
Surgical morbidity following neoadjuvant immunotherapy
Surgical complication rates according to Clavien-Dindo classification
Measured: Up to 1 year after start of treatment
Description of associations of TMB, fs/INDELs, HERVE-E, RNA tumor/immune signatures, and surface marker expression with tumor immune infiltrates and response
Measured: Up to 5 years after start of treatment
Cell free methylated DNA profiles following neoadjuvant immunotherapy between baseline and surgery
Measured: At 6 weeks
Collection of fresh tumor tissue for investigating TIL, scRNA and TCRseq
Measured: At 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2021
- Study start28 Apr 2022
- Primary completion22 Apr 2025
- Study completionApr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cell CarcinomaStudies 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Open-label three-arm randomized phase II trial
- Masking
- None (open label)
- Enrolment
- 69 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- John Haanen, Prof, Principal investigator, Medical oncologist/researcherAxel Bex, Prof, Principal investigator, Urologist/researcher
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05148546
- Sponsor's protocol ID
- M21NSC
- Other IDs
- CA209-6DJ, 2021-002360-51
- Acronym
- NESCIO
- Status last verified
- Sep 2025
- First submitted
- 25 Nov 2021
- Last updated
- 30 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Randomized, Neoadjuvant Phase II Study With Combination Immuno-oncology in Primary Clear Cell Renal Cancer at Risk for Recurrence or Distant Metastases (NESCIO-trial)
- ClinicalTrials.gov ID
- NCT05148546
- Acronym / sponsor ID
- NESCIO / M21NSC
- Conditions
- Renal Cell Carcinoma
- Keywords
- Resectable renal cell carcinoma, Checkpoint inhibition, Immunotherapy, PD-1 inhibitor, CTLA-4 inhibitor, LAG-3 inhibitor, Nivolumab, Ipilimumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 69 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 28 Apr 2022 (actual)
- Primary completion
- 22 Apr 2025 (actual)
- Study completion
- Apr 2029 (estimated)
- First posted
- 8 Dec 2021 (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 NESCIO-trial is a multicenter, randomized, open-label, three-arm phase II trial investigating different combinations of neoadjuvant immunotherapy in patients with primary, resectable, intermediate to high-risk, clear-cell renal cell carcinoma. In this trial patients will be randomized 1:1:1 to receive either 2 cycles of nivolumab 360mg every 3 weeks (arm A), 2 cycles of ipilimumab 1 mg/kg + nivolumab 3 mg/kg every 3 weeks (arm B) or 2 cycles of relatlimab 360mg + nivolumab 360mg every 3 weeks (arm C), prior to surgery at week 7.
After 42 patients (14 per arm) have been recruited, an interim analysis will be performed to evaluate the observed efficacy and toxicity within each arm and either allow for early discontinuation of the treatment or continuing recruitment for the second stage. As the primary endpoint, the pathological response (decrease in tumor) will be evaluated. If at most one pathologic response in the primary tumor is observed, the treatment arm will be closed for insufficient activity on the primary tumor. If at least 2 pathologic responses are observed, 9 additional patients will be included to a total of 23 patients per cohort. A maximum of 69 patients will be recruited for this study.
Follow up will start at week 12 with a CT-scan according to the national/center's standard. Patients will be evaluated every 3 months by physical examination and lab testing for up to two years, thereafter according to institutional guidelines up to 5 years following surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Open-label three-arm randomized phase II trial
| Arm | Type | Receives |
|---|---|---|
| A: Neoadjuvant nivolumab | Experimental | Drug: Neoadjuvant nivolumabNeoadjuvant 2 cycles of nivolumab 360mg every 3 weeks |
| B: Neoadjuvant nivolumab + ipilimumab | Experimental | Drug: Neoadjuvant nivolumab, Drug: Neoadjuvant ipilimumabNeoadjuvant 2 cycles of nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks |
| C: Neoadjuvant nivolumab + relatlimab | Experimental | Drug: Neoadjuvant nivolumab, Drug: Neoadjuvant relatlimabNeoadjuvant 2 cycles of nivolumab 360mg + relatlimab 360mg every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Adults at least 18 years of age;
- World Health Organization (WHO) Performance Status 0 or 1;
- Histologically confirmed resectable clear cell RCC (measurable according to RECIST 1.1), that can be biopsied, and no history of distant metastases;
- Intermediate to high risk will be based on clinical TNM and biopsy nuclear grade. These are:
- No other malignancies, except adequately treated and a cancer-related life-expectancy of more than 5 years;
Key exclusion criteria (19 listed)
- Distantly metastasized RCC;
- Brain metastases (based on symptoms);
- Non-clear cell RCC;
- No measurable lesion according to RECIST 1.1;
- Subjects with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy;
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 |
|---|---|---|
| Neoadjuvant nivolumabAlso: OpdivoPatients will receive 2 cycles of nivolumab 360mg (arm A and C) or 3mg/kg (arm B) every 3 weeks followed by a nephrectomy. | Drug | A: Neoadjuvant nivolumab, B: Neoadjuvant nivolumab + ipilimumab, C: Neoadjuvant nivolumab + relatlimab |
| Neoadjuvant ipilimumabAlso: YervoyPatients will receive 2 cycles of ipilimumab 1mg/kg every 3 weeks followed by a nephrectomy. | Drug | B: Neoadjuvant nivolumab + ipilimumab |
| Neoadjuvant relatlimabPatients will receive 2 cycles of relatlimab 360mg every 3 weeks followed by a nephrectomy. | Drug | C: Neoadjuvant nivolumab + relatlimab |
Primary outcome
Pathologic response rate
Time frame: At 6 weeks
Pathologic response rate is defined as the proportion of patients demonstrating a complete pathologic or partial pathologic response, according to central revision (pathology of NKI)
10 secondary outcomes
Safety, measured by the frequency of immune-related adverse events leading to postponing of surgery for >2 weeks
Time frame: At 8 weeks
Objective response rate
Time frame: At 6 weeks
Recurrence Free Survival (RFS)
Time frame: Up to 5 years after start of treatment
Event-free Survival (EFS)
Time frame: Up to 5 years after start of treatment
Rate of distant metastases
Time frame: Up to 5 years after start of treatment
Rate of local recurrences
Time frame: Up to 5 years after start of treatment
Surgical morbidity following neoadjuvant immunotherapy
Time frame: Up to 1 year after start of treatment
Description of associations of TMB, fs/INDELs, HERVE-E, RNA tumor/immune signatures, and surface marker expression with tumor immune infiltrates and response
Time frame: Up to 5 years after start of treatment
Cell free methylated DNA profiles following neoadjuvant immunotherapy between baseline and surgery
Time frame: At 6 weeks
Collection of fresh tumor tissue for investigating TIL, scRNA and TCRseq
Time frame: At 6 weeks
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 30 Sep 2025.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
John Haanen, Prof principal investigator
Medical oncologist/researcher
Axel Bex, Prof principal investigator
Urologist/researcher
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neoadjuvant nivolumab, Neoadjuvant ipilimumab and Neoadjuvant relatlimab in people with Renal Cell Carcinoma, run by The Netherlands Cancer Institute at 2 sites in 2 countries.
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 18 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 30 Sep 2025. 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 Netherlands, United Kingdom. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic response rate (time frame: At 6 weeks). 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 30 Sep 2025.