Two cycles of dual neoadjuvant immunotherapy (nivolumab/ipilimumab or nivolumab/relatlimab) induced high pathological response (pCR) rates in patients with triple-negative breast cancer (TNBC) harboring high numbers of tumor-infiltrating lymphocytes (TILs), results from two cohorts in the phase 2 BELLINI trial demonstrated.

PD-1 inhibition added to neoadjuvant chemotherapy has improved survival in early patients with TNBC¹; however, this comes with substantial toxicity. Patients TNBC with high levels of TILs have excellent survival, even without chemotherapy, while other solid tumors combination checkpoint blockade showed favorable outcomes compared with anti-PD1 monotherapy^2,3.

The phase 2 BELLINI trial (NCT03815890) aimed to evaluate the efficacy of neoadjuvant immunotherapy combinations in patients with TIL-high TNBC. Iris Nederlof, MD, from the Netherlands Cancer Institute, presented results from two combination cohorts: nivolumab/ipilimumab and nivolumab/relatlimab⁴. Both cohorts enrolled 15 participants (TILs ≥50%) who received either two cycles of nivolumab/ipilimumab (QW3) followed by resection, 6 weeks after the start of the therapy or two cycles of nivolumab/relatlimab (QW4) followed by resection, 8 weeks after the start of the therapy. The primary endpoint of the study was pCR.

In the nivolumab/ipilimumab cohort, five participants obtained pCR (33%) and three obtained near pCR, resulting in a rate of 53% obtaining major pathological response (MPR), a secondary endpoint. In the nivolumab/relatlimab cohort, seven participants obtained pCR (47%) and four obtained near pCR, so the MPR rate was 73%. In both cohorts, neoadjuvant dual immunotherapy came with a high incidence of immune-related AEs (100% any grade, 40–47% grade 3-4), e.g. hypothyroidism, adrenal gland insufficiency, and hepatitis. No delay of surgery was observed in either cohort.

“These promising pCR rates met the threshold to expand our cohorts to stage II. However, the high rates of immune-related AEs need further research on the QOL effect of these therapies,” Dr. Nederlof concluded.

Medical writing support was provided by Marten Dooper.

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