Patients with triple-negative breast cancer (TNBC) may be more likely to respond to immune checkpoint inhibitor (ICI) therapy if they have higher concentrations of tumor-infiltrating lymphocytes (TILs), according to research presented at ESMO Congress 2022.

These results come from the phase 2 BELLINI trial ( Identifier: NCT03815890), a basket trial of patients with TNBC and varying levels of TILs. Patients in the first basket received 4 weeks of nivolumab monotherapy, and those in the second basket received 4 weeks of dual therapy with nivolumab plus ipilimumab.

Each basket contained 15 patients, with 5 patients from each TIL level group — TIL low (5%-10%), TIL intermediate (11%-49%), and TIL high (³50%). After completing ICI therapy, patients in each basket went on to neoadjuvant chemotherapy or surgery.

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At baseline, the median age was 48 (range, 27-71) years in the monotherapy cohort and 50 (range, 34-67) years in the dual ICI cohort. Most patients in both groups had grade 3 tumors (93.8% and 73.3%, respectively). Patients in the monotherapy group were more likely than those in the dual therapy group to have no nodal involvement (81.3% and 33.3%, respectively).

At 4 weeks, partial radiologic responses were observed in 27% of the dual therapy cohort and 19% of the monotherapy cohort. Of the 7 responders, 3 patients had high TIL levels, and 4 had intermediate TIL levels.

The researchers also performed biopsies at 4 weeks and found no tumor cells in samples from 6 of the nivolumab-ipilimumab recipients and 1 of the nivolumab monotherapy recipients.

The researchers assessed immune activation at 4 weeks as well. They found a 2-fold increase in CD8 and/or interferon-gamma (IFNg) expression in 53.3% of patients in the monotherapy cohort and 60.0% of those in the dual therapy cohort.

When patients were stratified by radiologic response, responders had higher expression of IFNg (P =.014) and closer proximity between tumor cells and CD8 T cells (P =.0014).

The researchers also found that 24% of patients had clearance of circulating tumor DNA at 4 weeks.

Grade 1-2 treatment-related adverse events (TRAEs) occurred in 93% of dual ICI recipients and 81% of monotherapy recipients. Grade 3-4 TRAEs occurred in 7% and 6%, respectively. The most common TRAE was thyroid dysfunction, which was observed in 60% of the nivolumab-ipilimumab recipients and 50% of the nivolumab monotherapy recipients.

Disclosures: This study was supported by Bristol Myers Squibb and Natera. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.


Kok M, Nederlof I, Isaeva O, et al. Nivolumab and ipilimumab in early-stage triple negative breast cancer (TNBC) with tumor-infiltrating lymphocytes (TILs): First results from the BELLINI trial. Presented at ESMO 2022; September 9-13, 2022. Abstract LBA13.