Nivolumab in combination with ipilimumab [NIV9]

For the 1st line treatment of intermediate or poor risk advanced renal cell carcinoma where the following criteria are met:

1. This application is being made by and the first cycle of systemic anti-cancer therapy with the combination of nivolumab and ipilimumab will be prescribed by a consultant specialist specifically trained and accredited in the use of systemic anti-cancer therapy.
2. The patient has unresectable locally advanced or metastatic renal cell carcinoma (RCC) which has either a clear cell component or is one of the types of RCC as indicated below. Please indicate below which RCC histology applies to this patient:

• RCC with a clear cell component or
• Papillary RCC or
• Chromophobe RCC or
• Collecting duct RCC (Bellini collecting duct RCC) or
• Medullary RCC or
• Mucinous tubular and spindle cell RCC or
• Multilocular cystic RCC or
• XP11 translocation RCC or
• Unclassified RCC

3. The patient has intermediate or poor risk advanced renal cell carcinoma as assessed by the International Metastatic RCC Database Consortium (IMDC) system which scores 1 point for each of the following 6 factors – a score of 0 indicates good risk disease, a score of 1-2 indicates intermediate risk and a score of 3-6 denotes poor risk: The IMDC factors are:

• less than 1 year from time of initial diagnosis of RCC to now
• a Karnofsky performance status of <80% (see below for description of Karnofsky scale of performance status)
• the haemoglobin level is less than the lower limit of normal
• the corrected calcium level is >2.5mmol/L
• the platelet count is greater than the upper limit of normal
• the absolute neutrophil count is greater than the upper limit of normal. Please indicate below whether the patient is in the intermediate or poor risk prognostic group.
• intermediate risk disease (IMDC score of 1 or 2) or
• poor risk disease (IMDC score of 3-6)

Note

Note: IMDC favourable risk disease (IMDC score of 0) did worse with the combination of nivolumab and ipilimumab versus sunitinib in the Checkmate 214 study and thus the use of nivolumab plus ipilimumab is not licensed in the IMDC favourable risk population.

4. The patient is either completely treatment naïve for systemic immune-modulatory therapy for RCC or if the patient has received prior systemic immune-modulatory therapy in the context of adjuvant/neoadjuvant therapy, then such treatment was completed 12 or more months previously and the patient meets all other criteria listed here. Please mark below whether or not previous systemic immune-modulatory therapy has been received in the adjuvant/neoadjuvant setting:

• no previous adjuvant/neoadjuvant systemic immune-modulatory therapy of any kind and the patient is treatment naïve for the locally advanced/metastatic RCC indication or
• prior adjuvant/neoadjuvant therapy with immune-modulatory therapies for RCC anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD L2, anti-CD137 or anti-cytotoxic T lymphocyte associated antigen-4 (anti-CTLA-4) antibodies and last dose received by the patient was 12 or more months prior to this application and the patient is treatment-naïve for the locally advanced/metastatic RCC indication Please mark in the box the time since end of treatment with adjuvant/neoadjuvant immune-modulatory therapy: ________

5. The patient has a Karnofsky performance status of at least 70%. The relevant part of the Karnofsky performance status scale is as follows: 100% Normal, no complaints. No signs or symptoms of disease. 90% Able to carry on normal activities. Minor signs or symptoms of disease. 80% Normal activity with effort. Some signs or symptoms of disease. 70% Cares for self. Unable to carry on normal activity or to do active work. 60% Requires occasional assistance, but is able to care for most personal needs. 50% Requires considerable assistance and frequent medical care.
6. The patient has no symptomatic brain metastases or leptomeningeal metastases currently requiring steroids for symptom control.
7. The patient is to be treated until loss of clinical benefit or excessive toxicity or patient choice, whichever is the sooner.

Note

Note: there is no stopping rule as to the maximum treatment duration of nivolumab in this indication.

8. Ipilimumab will be used at the RCC ipilimumab dose of 1mg/Kg every 3 or 12 weeks for a maximum of four cycles. Combination treatment can be given as four 3-weekly cycles or as four 12-weekly cycles in accordance with the PRISM trial data (JCO 2023 42 312-325). In this situation maintenance single agent nivolumab can be commenced between extended dosing combination treatment as IV or SC dosing. All combination treatments must use appropriate dose IV nivolumab. Patients participating on the REFINE trial cannot be treated on extended interval combination dosing.
9. Nivolumab will be used at a dose of 3mg/Kg IV every 3 weeks for the first 4 cycles (i.e. when in combination with ipilimumab) and then as subsequent monotherapy at the licensed dose, frequency, and route for this indication, as shown below • Subcutaneously – at a dose of 600mg every 2 weeks, or 1200mg every 4 weeks • Intravenously – at a dose of 240mg every 2 weeks, or 480mg every 4 weeks • 480mg IV every 8 weeks, ONLY if the patient is participating in the REFINE trial (NIHR CPMS ID 50169). • 1200mg SC every 8 weeks ONLY if the patient is participating in the REFINE trial (NIHR CPMS ID 50169).
10. Nivolumab and ipilimumab will be prescribed and administered as outlined in their respective Summary of Product Characteristics (SPCs) for this indication.
11. When a treatment break of more than 12 weeks beyond the expected 2-, 3-, or 4-weekly cycle length is needed, I will complete a treatment break approval form requesting a restart of treatment. This must be approved before ipilimumab and/or nivolumab are re-commenced
12. If the disease progresses on the nivolumab plus ipilimumab combination the next set of treatment options are those drugs which are routinely commissioned as first to be used VEGF- or VEGFR-targeting drugs ie one choice of the following: cabozantinib or pazopanib or tivozanib or sunitinib.

NHS funded From: 21 June 2022

Additional information

Form version: -

CDF Managed Access: NA

NICE Technology Appraisal: TA780 (23 March 2022)

Current Form Version

Note

The data on this page was produced using version 1.387 of the CDF list, downloaded from NHS England’s website on 24 February 2026 at 11:00.

If NHS England has published a new version of the CDF List but this site has not yet accessed that, this form may be out of date. Additionally, if any update has occurred without NHS England noting it as a change, this page will be out of date.

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• NIV9_prior_to_cdf_1.364
• NIV9_prior_to_cdf_1.380