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

Breast Cancer Clinical Trial

— BELLINI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03815890
• Other study ID #: M18BEL
• Status: Recruiting
• Phase: Phase 2
• Start date: October 4, 2019
• Est. completion date: January 1, 2033

Study information

• Verified date: May 2024
• Source: The Netherlands Cancer Institute
• Contact: M Kok, MD
• Phone: 3120512
• Email: m.kok[@]nki.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 1, 2033
• Est. primary completion date: January 1, 2031
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
Netherlands	NKI-AVL	Amsterdam

Sponsors (2)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute	Bristol-Myers Squibb

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response rate per cohort,	number of patients with no residual invasively growing tumor cells detected by microscopic examination in breast and axilla	up to 3 weeks after surgery, an average of 6 months
Secondary	Incidence of Treatment-Emergent Adverse Events according to NCI Common Toxicity Criteria version 5.0	Adverse events in all regimens will be graded according to NCI Common Toxicity Criteria version 5.0.	up to 3 weeks after surgery, an average of 6 months
Secondary	Radiological response rate	The percentage of patients having a complete response, partial response or stable disease per cohort assessed by MRI	At 4 weeks
Secondary	Immune activation after pre-operative nivolumab, either as monotherapy or in combination with ipilimumab or relatlimab or novel IO combinations.	Immune activation is defined as either a 2-fold increase in tumor-associated CD8 after pre-operative immunotherapy; and/or a 2-fold increase expression of genes induced by IFNy (determined using mRNA expression levels)	within 6 months after surgery