Pre-operative Trial for Breast Cancer With Nivolumab in Combination With Novel IO

Официальное название

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

Обзор

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.

Подробное описание

The investigators aim to test the activity of nivolumab monotherapy in primary breast tumors in a pre-operative window of opportunity trial. As the data of the investigators generated in the TONIC trial (metastatic TNBC) indicate that low dose doxorubicin may 'prime' the tumor microenvironment (TME) resulting in higher response rates on nivolumab, in addition, cohorts for treatment with nivolumab plus low dose doxorubicin will be opened. Given the emerging data on other immunomodulatory strategies, this platform study allows opening additional cohorts for promising novel immune-oncology (IO) drugs for which a strong efficacy signal has been seen without drug safety issues. The investigators will study the TME and systemic host factors with specific emphasis on immunosuppressive processes that can potentially be targeted by novel IO agents to further optimize BC immunotherapy.

Вмешательства

• Препарат Nivolumab
  2 courses 240 mg flat dose
• Препарат Ipilimumab
  single dose ipilimumab (1mg/kg) at day 1
• Препарат Ipilimumab
  two courses ipilimumab (1mg/kg) at day 1 and 21

Первичные конечные точки

• Pathological complete response rate per cohort, [Срок оценки: up to 3 weeks after surgery, an average of 6 months]

Вторичные конечные точки (3)

• Incidence of Treatment-Emergent Adverse Events according to NCI Common Toxicity Criteria version 5.0 [Срок оценки: up to 3 weeks after surgery, an average of 6 months]
• Radiological response rate [Срок оценки: At 4 weeks]
• Immune activation after pre-operative nivolumab, either as monotherapy or in combination with ipilimumab or relatlimab or novel IO combinations. [Срок оценки: within 6 months after surgery]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• NKI-AVL — Amsterdam

Публикации

• Nederlof I, Isaeva OI, de Graaf M, Gielen RCAM, Bakker NAM, Rolfes AL, Garner H, Boeckx B, Traets JJH, Mandjes IAM, de Maaker M, van Brussel T, Chelushkin M, Champanhet E, Lopez-Yurda M, van de Vijver K, van den Berg JG, Hofland I, Klioueva N, Mann RM, Loo CE, van Duijnhoven FH, Skinner V, Luykx S, Kerver E, Kalashnikova E, van Dongen MGJ, Sonke GS, Linn SC, Blank CU, de Visser KE, Salgado R, Wess PMID 39284953

Идентификаторы

NCT: NCT03815890 · M18BEL

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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