Pre-operative Phase II Trial for Breast Cancer With Nivolumab in Combination With Novel IO (BELLINI Trial)

M18BEL

To determine whether short-term pre-operative nivolumab either as monotherapy or in combination with low dose doxorubicin or novel IO combinations can induce immune activation in early BC.

2019-10-04

2031-01-01

2033-01-01

Recruiting

Early phase I

80

Inclusion Criteria: * Signed written informed consent * 18 years or older at moment of inclusion; * Female gender; * WHO performance status 0 or 1; * Resectable primary breast cancer stage I-III. Nodal status must be examined by ultrasound, fine needle aspiration, sentinel node biopsy, or FDG-PET scan. * The tumors must be: * at least 10 mm (minimum cT1c) as determined by MRI * TNBC defined as ER\<10%, HER2-negative OR luminal B defined as ER≥10%, HER2-negative with either Ki67≥20% or PR =\<20% OR grade 3. HER2 negative is defined as an IHC score of \<2 or 2+ with a negative ISH. * For TNBC patients: TIL≥5% * For LumB breast cancer patients: TIL≥1% * For cohort 3B: N0 status, TN and TIL ≥50% * For cohort 4B: N0 status, TNBC and TIL 30-49% * For cohort 5B: N0 status, TNBC and TIL ≥50% ● Patients with multifocal/multicentric breast cancer are eligible if triple negative breast cancer histology as well as sufficient TIL percentages (30-49% in cohort 4B, ≥50% in cohort 5B) have been confirmed in all tumor lesions. Exclusion Criteria: * evidence or suspicion of metastatic disease. Evaluation of the presence of distant metastases may include chest X-ray, liver ultrasound, isotope bone-scan, CT-scan of chest and abdomen and/or FDG-PET scan, according to local procedures; * evidence of a concurrent contralateral or ipsilateral second primary infiltrating breast cancer. Evaluation of the presence of a concurrent second primary breast cancer may include mammography, breast ultrasound and/or MRI breast; * other malignancy except carcinoma in situ and basal-cell and squamous carcinoma of the skin, unless the other malignancy was treated ≥5 years ago with curative intent without the use of chemotherapy or radiotherapy * previous radiation therapy or chemotherapy; * prior treatment with checkpoint inhibitors (including anti- PD1, -PD-L1, -CTLA-4); * concurrent anti-cancer treatment, neoadjuvant therapy or another investigational drug;

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Separate cohorts will be opened in this trial. LumB and TNBC tumors will be divided in separate cohorts.More cohorts, e.g. combining nivolumab and novel IO, can open after the start of this trial.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 80, 'type': 'ESTIMATED'}}

2024-05-30