Clinical trial NCT03815890: Pre-operative Trial for Breast Cancer With Nivolumab in Combination With Novel IO
Official title: Pre-operative Phase II Trial for Breast Cancer With Nivolumab in Combination With Novel IO (BELLINI Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Keywords: pre-operative
triple negative and Luminal B
resectable, stage I-III
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2019-01-24
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

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;

Primary outcomes:
measure: Pathological complete response rate per cohort,
timeFrame: up to 3 weeks after surgery, an average of 6 months
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events according to NCI Common Toxicity Criteria version 5.0
timeFrame: up to 3 weeks after surgery, an average of 6 months
measure: Radiological response rate
timeFrame: At 4 weeks
measure: Immune activation after pre-operative nivolumab, either as monotherapy or in combination with ipilimumab or relatlimab or novel IO combinations.
timeFrame: within 6 months after surgery
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: NKI-AVL
Study officials:
affiliation: NKI-AvL
name: M Kok, MD
role: PRINCIPAL_INVESTIGATOR
References: