Pre-operative treatment for breast cancer using nivolumab and novel immunotherapies

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

This study is testing whether a new combination of immunotherapy treatments can help boost the immune response in patients with early-stage breast cancer before surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: The Netherlands Cancer Institute (other)
• Drugs / interventions: chemotherapy, radiation, nivolumab, doxorubicin, immunotherapy
• Locations: 1 site (Amsterdam)
• Trial ID: NCT03815890 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of nivolumab, both alone and in combination with low-dose doxorubicin or other novel immuno-oncology agents, in inducing immune activation in patients with early-stage breast cancer. The study focuses on patients with resectable triple-negative and Luminal B breast cancer, assessing the tumor microenvironment and systemic factors that may influence treatment response. By utilizing a pre-operative window of opportunity, the trial seeks to optimize immunotherapy strategies for breast cancer patients. The study will also explore the potential of various immunomodulatory approaches to enhance treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates for this study are female patients aged 18 or older with resectable primary breast cancer stages I-III, specifically those with triple-negative or Luminal B subtypes.

Not a fit: Patients with non-resectable breast cancer or those with HER2-positive tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could lead to improved immune responses and better treatment outcomes for patients with early-stage breast cancer.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches, indicating potential for success in this trial.

Eligibility criteria

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;

Where this trial is running

Amsterdam

• NKI-AVL — Amsterdam, Netherlands (RECRUITING)

Study contacts

• Principal investigator: M Kok, MD — NKI-AvL
• Study coordinator: M Kok, MD

Conditions: Breast Cancer, pre-operative, triple negative and Luminal B, resectable, stage I-III