Nivolumab and ipilimumab with tumour-infiltrating lymphocytes to treat triple-negative breast cancer

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Published: 12 Sep 2022
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Dr Iris Nederlof - The Netherlands Cancer Institute, Amsterdam, Netherlands

Dr Iris Nederlof speaks to ecancer about the BELLINI trial which explores the treatment of nivolumab and ipilimumab in early-stage triple-negative breast cancer (TNBC) with tumour-infiltrating lymphocytes (TILs). The study’s main idea originated from immune checkpoint blockade (ICB) added to neoadjuvant chemotherapy (CTx) improving the outcome for early-stage TNBC patients.

The method followed a primary endpoint of immune activation defined as 2-fold change in CD8+ T cells or 2FC IFNG expression increasing after 4 weeks. Secondary endpoints included safety, radiological response and translational analyses. 

Results of the BELLINI trial found that the majority of TNBC patients with TILs showed increased immune activation after only 4 weeks of ICB and a substantial fraction experienced a clinical response, highlighting the potential of ICB without CTx for TNBC patients.


BELLINI is a phase II window of opportunity trial where we treat patients with early stage triple-negative breast cancer, meaning that they didn’t receive any therapy when they are enrolled in the trial. We looked at whether or not patients that have early triple-negative breast cancer can reach immune activation when they receive nivolumab or nivolumab and ipilimumab for four weeks before the start of chemotherapy or surgery. So it was purely a translational endpoint to see what the potential of immunotherapy is in this patient population.

How many patients were involved in this trial?

We so far enrolled 31 patients that we presented here at ESMO. We are also enrolling more patients in more cohorts because it’s a basket trial so we can open more cohorts during the time of the trial. So, so far we are enrolling more patients.

What have you found so far?

So far we have found that if we give four weeks of neoadjuvant immunotherapy without chemotherapy that approximately half of the patients can reach an immune activation, so a doubling of CD8 T-cells or interferon-gamma. That was also the endpoint of the trial. So we wanted to see one-third of immune activation, that was the primary endpoint, and we see it in half of the patients. So, so far, so good.

What can we do with this information?

What can we do? What we can do with this information is to look better if patients that currently have early triple-negative breast cancer need both immunotherapy and chemotherapy because that’s the standard of care. It’s a great step forward for all patients but also it’s not really precision medicine because now we treat all the patients the same, in the same manner. We believe there is a subgroup of triple-negative breast cancer patients that probably don’t need both of these therapies. Either they don’t need immunotherapy because they won’t respond or maybe they don’t need chemotherapy because immunotherapy is enough for these patients. 

So we should be identifying these patients?

Yes, that would be great. If we can up-front identify these patients and in the future we can say, ‘You probably only need chemotherapy,’ ‘You need immunotherapy,’ ‘You need both,’ or maybe, ‘You don’t even need therapy.’ Because if you have a highly immunogenic tumour maybe you don’t even need systemic therapy to have an excellent prognosis. I think that would be great for the future if we can start selecting patients for the right systemic therapy.