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

NCT ID: NCT03815890

Last Updated: 2024-05-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-04
• Study Completion Date: 2033-01-01

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1A; LumB

Nivolumab

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

2 courses 240 mg flat dose

1B; TNBC

Nivolumab

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

2 courses 240 mg flat dose

2A; LUMB

Nivolumab and ipilimumab

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

2 courses 240 mg flat dose

Ipilimumab

Intervention Type: DRUG

single dose ipilimumab (1mg/kg) at day 1

2B; TNBC

Nivolumab and ipilimumab

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

2 courses 240 mg flat dose

Ipilimumab

Intervention Type: DRUG

single dose ipilimumab (1mg/kg) at day 1

3B; TNBC, High TIL

Nivolumab and ipilimumab

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

2 courses 240 mg flat dose

Ipilimumab

Intervention Type: DRUG

two courses ipilimumab (1mg/kg) at day 1 and 21

Interventions

Nivolumab

2 courses 240 mg flat dose

Intervention Type: DRUG

Ipilimumab

single dose ipilimumab (1mg/kg) at day 1

Intervention Type: DRUG

Ipilimumab

two courses ipilimumab (1mg/kg) at day 1 and 21

Intervention Type: DRUG

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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

M Kok, MD

Role: PRINCIPAL_INVESTIGATOR

NKI-AvL

Locations

NKI-AVL

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

M Kok, MD

Role: CONTACT

m.kok@nki.nl

3120512 ext. 9111

I Nederlof

Role: CONTACT

i.nederlof@nki.nl

3120512 ext. 9111

Facility Contacts

M Kok, MD

Role: primary

m.kok@nki.nl

I Nederlof

Role: backup

i.nederlof@nki.nl

References

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, Wessels LFA, Drukker CA, Schumacher TN, Horlings HM, Lambrechts D, Kok M. Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial. Nat Med. 2024 Nov;30(11):3223-3235. doi: 10.1038/s41591-024-03249-3. Epub 2024 Sep 16.

Reference Type: DERIVED

PMID: 39284953 (View on PubMed)

Other Identifiers

M18BEL

Identifier Type: -

Identifier Source: org_study_id