LBA11 - Neoadjuvant nivolumab/relatlimab or nivolumab/ipilimumab in triple negative breast cancer with high tumor-infiltrating lymphocytes (TILs)

Background

For triple negative breast cancer (TNBC) the addition of immunotherapy to chemotherapy improves the pathological complete response (pCR) rate and outcome. However, chemotherapy plus immunotherapy comes with substantial toxicity warranting exploration of de-escalation approaches. Currently, it is unknown what the pCR rate is for TNBC when immunotherapy is given without chemotherapy. Patients with TNBC and high TILs have an excellent prognosis even without chemotherapy justifying testing de-escalation. Previous cohorts in our phase II BELLINI platform trial showed immune activation when using (combination) immunotherapy without chemotherapy. Here we present two new non-randomized cohorts with short-term neoadjuvant combination immunotherapy in patients with TNBC and high TILs with pCR as primary endpoint.

Methods

Patients with stage I-II, node negative, TILs ≥50% TNBC were treated with 6-weeks nivolumab plus ipilimumab 1mg/kg (d1 + d21, n = 15) or 8-weeks nivolumab plus relatlimab (anti-LAG3) (d1 + d29, n=15) before surgery. Radiological non-responders at 6 weeks in the nivo/rela cohort proceeded to neoadjuvant chemotherapy and were counted as non-responders. Secondary endpoints include major pathological response (MPR) defined as ≤10% residual viable tumor, radiological response rate assessed by MRI and safety.

Results

We observed a pCR in 5/15 (33%) patients and a MPR in 8/15 (53%) patients in the nivo/ipi cohort. The nivo/rela cohort showed a pCR in 7/15 (47%) patients and a MPR in 11/15 (73%) patients. In total, 8 (26.7 %) patients developed grade 3-4 adverse events, of which 6 received nivo/ipi. Most common adverse events included endocrinopathies: hypothyroidism (40.0% in nivo/ipi, 33.3% in nivo/rela), adrenal insufficiency (26.7% in nivo/ipi, 6.7% in nivo/rela) and diabetes (6.7% in nivo/rela).

Conclusions

We present the first exploratory clinical trial with short-term neoadjuvant immunotherapy without chemotherapy for patients with TNBC with high TILs and observed a pCR rate of 33% with nivo/ipi and 47% with nivo/rela, warranting further studies on efficacy and toxicity of chemotherapy-free immunotherapy for immunogenic TNBC.

Clinical trial identification

NCT03815890 Release date: 18-02-2019.

Editorial acknowledgement

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

Bristol Myers Squibb.

Disclosure

G. Awada: Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Funding: Novartis, Stichting tegen Kanker, Kom op tegen Kanker; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: ESMO, FWO, Gilead Sciences, Pierre Fabre; Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Biocartis. H.M. Horlings: Financial Interests, Institutional, Other, Research support: Roche. K. Van De Vijver: Financial Interests, Institutional, Advisory Board, and speakers fee: GSK, Owkin, Exact Sciences, AstraZeneca; Financial Interests, Other, Travel and accommodation: GSK. R.M. Mann: Financial Interests, Research Grant: Siemens Healthineers, Bayer Healthcare, Screenpoint Medical, Beckton & Dickinson, PA Imaging, Lunit and Koning; Financial Interests, Advisory Board, member: Screenpoint, Bayer, Siemens, Guerbet. C.U. Blank: Financial Interests, Funding: BMS, Novartis, NanoString, 4SC; Financial Interests, Institutional, Speaker, Consultant, Advisor: BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre; Financial Interests, Personal, Speaker, Consultant, Advisor: Third Rock Venture; Financial Interests, Other, Stock/stock options: Immagene BV, Signature Oncology. T.N. Schumacher: Financial Interests, Other, Venture partner: Third Rock Ventures; Financial Interests, Advisory Role, also stockholder: Allogene Therapeutics, Merus, Scenic Biotech; Financial Interests, Advisory Role, also founder, also stockholder: Asher Bio, Cell Control, Neogene Therapeutics. R.F. Salgado: Financial Interests, Personal, Advisory Board: Roche, BMS, Exact Sciences, Daichhi Sankyo, AstraZeneca; Financial Interests, Personal, Invited Speaker: Daichii Sankyo, AstraZeneca; Financial Interests, Personal, Funding, Roche funded personally the assessment of immune-markers in a research study. This was in 2019: Roche; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Funding: Puma Biotechnology. M. Kok: Financial Interests, Institutional, Research Funding: BMS, Roche, AstraZeneca; Financial Interests, Institutional, Advisory Role: AstraZeneca, Daiichi Sankyo, Domain Therapeutics, Alderaan, BMS, MSD, Roche; Financial Interests, Institutional, Speaker, Consultant, Advisor, Speakers’ fee compensated to the institute: Roche, BMS, Gilead. All other authors have declared no conflicts of interest.