Pre-operative phase II trial for breast cancer with nivolumab in combination with novel IO (BELLINI trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Aug 2019 → ongoing

Decision date (initial)

2024-12-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bristol Myers Squibb

External identifiers

EU CT number

2024-515080-54-00

EudraCT number

2018-004188-30

ClinicalTrials.gov

NCT03815890

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Therapy, Efficacy, Safety

To determine whether short-term pre-operative nivolumab either as monotherapy or in combination with ipilimumab or relatlimab or novel IO combinations can induce pathological complete response

Secondary objectives 7

1. ● To establish whether short-term pre-operative nivolumab either as monotherapy or in combination with low dose ipilimumab or novel IO combinations is safe in early BC patients
2. ● To assess the proportion of clinical and radiological responses as measured by morphological and metabolic imaging
3. ● To assess the proportion of pathological responses (pCR, residual cancer burden)
4. ● To correlate parameters of systemic immune suppression in early BC with intratumoral immune landscape and with responses seen in patients
5. ● To correlate changes in tumor fragments (ex vivo model system, developed by Daniela Thommen) upon nivolumab either as monotherapy or in combination with ipilimumab or novel IO combinations with changes in the post-treatment surgical specimen or biopsy
6. ● To explore the putative predictive value of upcoming biomarkers such as but not limited to: CD8, IFNy gene signature, mutational load, homologous recombination deficiency (HRD)
7. ● To evaluate 3-year, 5-year and 10-year overall and event free survival rate

Conditions and MedDRA coding

Breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Signed written informed consent
2. 18 years or older at moment of inclusion
3. Female gender
4. WHO performance status 0 or 1
5. Resectable primary breast cancer stage I-III. Nodal status must be examined by ultrasound, fine needle aspiration, sentinel node biopsy, or FDG-PET scan (cohort 3B, 4B ,5B and 2A and 3A: PET-CT mandatory).
6. The tumors must be: >5 mm (minimum cT1b) as determined by MRI. TNBC (all cohorts B) defined as ER<10%, HER2-negative. Luminal B (cohort 1A) defined as ER≥10%, HER2- negative with either Ki67≥20% or PR ≤20% OR grade 3 AND TIL ≥1%. High-risk ER (cohort 2A and 3A) cT3-4N0 OR clinically node positive AND grade 3 OR grade 2 with ER levels of 50% or lower or TIL≥1%. For cohort 3B: N0 status, TNBC and TIL ≥50%. For cohort 4B: N0 status, TNBC and TIL 30-49%. For cohort 5B: N0 status, TNBC and TIL ≥50%.
7. Patients with multifocal/multicentric breast cancer are eligible if subtype 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 6

1. 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
2. other prior invasive malignancy 1) in the breast or 2) localized in the near proximity of the breast, that was treated with radiotherapy at the localization of the new breast tumor
3. occult breast cancer
4. previous anti-cancer hormone therapy or chemotherapy
5. prior treatment with checkpoint inhibitors (including anti-PD1, -PD-L1, -CTLA-4, -LAG3)
6. concurrent anti-cancer treatment, neoadjuvant therapy or another investigational drug (except for neoadjuvant chemotherapy in cohort 2A / 3A)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. pathological complete response rate per cohort, with a pCR defined as no residual invasively growing tumor cells detected by microscopic examination in breast and axilla.

Secondary endpoints 5

1. incidence, nature and severity of Adverse Events graded according to NCI-CTCAE v5.0 collected during treatment and up to 3 weeks post-surgery.
2. Radiological response using breast MRI per cohort
3. Event-free survival (EFS)
4. Overall survival (OS)
5. Immune activation after pre-operative nivolumab, either as monotherapy or in combination with ipilimumab or relatlimab or novel IO combinations

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Marleen Kok

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Marleen Kok

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications