Published

April 20, 2025

Cabozantinib in combination with nivolumab [CABNIV1]

For use in treatment-naïve patients with intermediate or poor risk advanced renal cell carcinoma for whom combination treatment with either nivolumab plus ipilimumab or lenvatinib plus pembrolizumab would otherwise be suitable where the following criteria have been met:

  1. This application is being made by and the first cycle of systemic anti-cancer therapy with the combination of cabozantinib plus nivolumab will be prescribed by a consultant specialist specifically trained and accredited in the use of systemic anti-cancer therapy.
  2. The prescribing clinician is fully aware of the management of and the treatment modifications that may be required for immune-related adverse reactions due to checkpoint inhibitor treatments including pneumonitis, colitis, nephritis, endocrinopathies, hepatitis, skin toxicity and other immune-related adverse reactions.
  3. 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
  • Mucinous tubular and spindle cell RCC or
  • Multilocular cystic RCC or
  • XP11 translocation RCC or
  • Unclassified RCC
  1. The patient has advanced RCC and the patient’s disease is in the intermediate or poor risk category as assessed by the International Metastatic RCC Database Consortium (IMDC) system which scores 1 point for each of the 6 factors listed below – 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%
  • 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: cabozantinib plus nivolumab is not approved for patients with good risk RCC.
  1. 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: _________
  1. In the absence of cabozantinib plus nivolumab, the patient would otherwise be suitable for combination treatment with either nivolumab plus ipilimumab or lenvatinib plus pembrolizumab. Note: NICE recommended cabozantinib plus nivolumab as an option only in those patients who would otherwise be suitable for either nivolumab plus ipilimumab or lenvatinib plus pembrolizumab but not in patients suitable for single agent TKI therapy.
  2. The patient has a Karnofsky performance status of at least 70 (ie an ECOG performance score of 0 or 1).
  3. The patient has no symptomatic brain metastases or leptomeningeal metastases currently requiring steroids for symptom control. 9.The patient is to be treated with cabozantinib until loss of clinical benefit or excessive toxicity or withdrawal of patient consent, whichever is the sooner. Note: there is no stopping rule as to the maximum treatment duration of the cabozantinib part of this indication. Note: if cabozantinib is permanently discontinued on account of toxicity, treatment with nivolumab can be continued as monotherapy as long as there is no evidence of progressive disease and the patient has not already completed 2 years of treatment with nivolumab.
  4. The patient is to be treated with nivolumab until loss of clinical benefit or excessive toxicity or withdrawal of patient consent or completion of a total treatment duration of 2 calendar years, whichever occurs first. 2 calendar years of treatment is defined as a duration of treatment which does not have any cycles of nivolumab in the period commencing on or after a date which is 2 years after the date of first nivolumab treatment. Note: if nivolumab is permanently discontinued on account of toxicity, treatment with cabozantinib can be continued as monotherapy as long as there is no evidence of progressive disease.
  5. A formal medical review to assess the tolerability of treatment with cabozantinib plus nivolumab will be scheduled to occur at least by the start of the 5th 2-weekly cycle or 3rd 4-weekly cycle of treatment and thereafter on a regular basis.
  6. When a treatment break of more than 12 weeks beyond the expected 2- or 4-weekly cycle length is needed, a treatment break approval form will be completed to restart treatment.
  7. If the disease progresses on the cabozantinib plus nivolumab combination and further systemic therapy is appropriate, the next line of treatment will be chosen from those options which are routinely commissioned ie for the next line of systemic therapy, there will be use of one choice of the following (mainly incorporating TKI options which have multiple modes of action): the currently commissioned 2nd line options of axitinib or lenvatinib plus everolimus or everolimus monotherapy or the currently commissioned 1st line options of sunitinib (still on label as 2nd line treatment) or pazopanib (off label as 2nd line treatment) or tivozanib (off label as 2nd line treatment).
  8. Cabozantinib and nivolumab will be otherwise prescribed and administered as outlined in their respective Summary of Product Characteristics (SPCs).

NHS funded From: 09 July 2024

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CDF Managed Access: NA

NICE Technology Appraisal: TA964 (10 April 2024)

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Note

The data on this page was produced using version 1.359 of the CDF list, downloaded from an archive of NHS England’s website on 11 April 2025 at 09:00.

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.