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

NCT03815890 | Recruiting Phase 2

• 1 other identifier: M18BEL
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

pre-operative; triple negative and Luminal B; resectable, stage I-III

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events according to NCI Common Toxicity Criteria version 5.0

  up to 3 weeks after surgery, an average of 6 months

• Radiological response rate

  At 4 weeks

• Immune activation after pre-operative nivolumab, either as monotherapy or in combination with ipilimumab or relatlimab or novel IO combinations.

  within 6 months after surgery

Study Arms (5)

1A; LumB

EXPERIMENTAL

Nivolumab

Drug: Nivolumab

1B; TNBC

EXPERIMENTAL

Nivolumab

Drug: Nivolumab

2A; LUMB

EXPERIMENTAL

Nivolumab and ipilimumab

Drug: Nivolumab; Drug: Ipilimumab

2B; TNBC

EXPERIMENTAL

Nivolumab and ipilimumab

Drug: Nivolumab; Drug: Ipilimumab

3B; TNBC, High TIL

EXPERIMENTAL

Nivolumab and ipilimumab

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

2 courses 240 mg flat dose

1A; LumB; 1B; TNBC; 2A; LUMB; 2B; TNBC; 3B; TNBC, High TIL

Ipilimumab DRUG

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

2A; LUMB; 2B; TNBC

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

NKI-AVL

Amsterdam, 1066CX, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 39284953 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• M Kok, MD

  NKI-AvL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

M Kok, MD

CONTACT

3120512; m.kok@nki.nl

I Nederlof

CONTACT

3120512; i.nederlof@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 13, 2018
• First Posted: January 24, 2019
• Study Start: October 4, 2019
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2033
• Last Updated: May 30, 2024

Record last verified: 2024-05

Locations

NL (1)