Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
110
Countries
1
Sites
1
Early stage triple negative breast cancer
To evaluate efficacy of two parallel cohorts of the neoadjuvant immune-chemotherapy (Nivolumab lead in vs concurrent) combination in participants with TNBC primary breast cancer
Key facts
- Sponsor
- ANZ Breast Cancer Trials Group Limited
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 27 Jan 2022 → 18 Jul 2025
- Decision date (initial)
- 2024-07-22
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Breast Cancer Trials, Australia and New Zealand · Bristol-Myers Squibb
External identifiers
- EU CT number
- 2024-512625-86-00
- EudraCT number
- 2019-003465-18
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Efficacy, Safety
To evaluate efficacy of two parallel cohorts of the neoadjuvant immune-chemotherapy (Nivolumab lead in vs concurrent) combination in participants with TNBC primary breast cancer
Secondary objectives 8
- To evaluate efficacy in the two cohorts in TNBC with higher TIL levels
- To evaluate efficacy in the two cohorts in TNBC that are PD-L1 positive
- To evaluate efficacy using other endpoints
- To investigate safety of the treatment combinations
- To determine associations between baseline TILs level as evaluated on diagnostic H&E slide and efficacy by cohort
- To determine associations between TIL values Days 8-14 by cohort and efficacy endpoints by cohort
- To determine association between change in TILs from baseline and Days 8-14 and efficacy endpoints by cohort
- To describe TIL levels in the persistent (residual) disease (ypINV Stage) according to RCB by cohort, and determine their associations with post-surgical outcomes
Conditions and MedDRA coding
Early stage triple negative breast cancer
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Nivolumab monotherapy lead in "window" or commencement of nivolumab concurrently with chemotherapy Nivolumab monotherapy lead in "window" or commencement of nivolumab concurrently with chemotherapy
|
Randomised Controlled | None | Arm A Nivolumab "Lead-In" window: Nivolumab 240 mg IV D1 lead in dose and 2 weeks later followed by Nivolumab 360 mg IV D1 Q3W x 4 with Carboplatin AUC5 D1 Q3W x 4 and Paclitaxel 80mg/m2 weekly x 12 as an IV infusion administered per institutional guidelines. Surgery will be performed 14-28 days after the last Paclitaxel dose Arm B – Concurrent Nivolumab with Nivolumab before Surgery: Nivolumab 360 mg IV D1 Q3W x 4 with Carboplatin AUC5 D1 Q3W x 4 and Paclitaxel 80 mg/m2 weekly x 12, followed three weeks after the prior nivolumab dose by single agent Nivolumab 240 mg IV D1. |
Regulatory references
- Scientific advice from competent authorities
- Italian Medicines Agency
- Plan to share IPD
- Yes
- IPD plan description
- General data sharing arrangements are documented in the protocol, PICFs, Data Management Plan and BCT SOPs. Applications for data sharing will be considered after publication of the main/final trial results.
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Female or male, age >= 18 years
- ECOG performance status 0-1
- Previously untreated non-metastatic (M0) TNBC meeting Stage I or II criteria as assessed by the local investigator on the basis of mammogram (MMG) and/or ultrasound (US) of the breasts, and US or clinical examination of the axilla. a) Stage I c T1c cN0; Stage IIA cT1 cN1; cT2 cN0; Stage IIB cT2 cN1; cT3 cN0
- Clinically node positive participants should undergo computed tomography (CT) scan or PET CT of chest/abdomen (and bone scan if clinically indicated) to exclude metastases.
- Non-metastatic, potentially operable, unilateral triple negative breast cancer, histologically defined as: a) ER negative: with < 1% of tumour cells positive for ER by IHC irrespective of staining intensity AND b) PR negative: with < 10% tumour cells positive for PR by IHC irrespective of staining intensity; AND c) HER2 negative: IHC 0 or 1+, or ISH (FISH or SISH) negative
- Able to start study treatment within 14 days of randomisation
- Surgery able to be undertaken within 4 weeks of final dose of neoadjuvant IV therapy. Pre-operative radiation is not permitted for any participant with operable cancer after final study treatment
- Adequate organ function. All screening laboratory tests should be performed within 14 days of randomisation.
Exclusion criteria 11
- Confirmed presence of AJCC 8th Edition anatomic Stage 3 or 4 disease
- Tumour of any size considered inoperable at presentation
- Multifocal or bilateral invasive breast cancer
- Has received prior chemotherapy, targeted therapy, radiation therapy, immunotherapy that target immune checkpoints, co-stimulatory or co-inhibitory pathways for T-cell receptors within the past 12 months
- Will be offered neoadjuvant breast radiation therapy
- Undergone or planned for sentinel lymph node biopsy before study therapy
- Currently participating and receiving study therapy or has participated in a study of an investigational therapeutic agent and received study therapy within 4 weeks before randomisation. Note: participant will be excluded if he/she received an investigational therapeutic agent with anticancer or anti-proliferative intent within the last 12 months
- Any concurrent anti-neoplastic therapy (i.e. chemotherapy, hormonal therapy, immunotherapy, extensive, non-palliative radiation therapy, or standard or investigational agents for treatment of breast cancer) not already specified in the protocol
- Prior malignancy active within the previous 3 years before randomisation, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
- Other active malignancy requiring concurrent intervention
- Has significant cardiovascular disease such as myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months, congestive cardiac failure NYHA classification IV or history of CHF NYHA III or IV
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Pathological complete response (pCR breast and nodes) as defined by ypT0/Tis/ypN0
Secondary endpoints 8
- Pathological complete response (pCR as defined by ypT0/Tis/ypN0) in the higher TIL subgroup (%TIL on baseline H&E 30% or more)
- Pathological complete response (pCR as defined by ypT0/Tis/ypN0) in the PD-L1 positive subgroup (defined as 1% or more immune cell staining using the Ventana SP142 assay)
- Pathological complete response (pCR) in breast (ypT0/Tis)
- Residual cancer burden (RCB)0/1
- Tumour response by WHO Criteria
- Ki67 proliferation marker changes between baseline and surgery
- Safety and tolerability as documented according to NCI-CTCAE V5.0
- Event free survival and overall survival over a 3-year period
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
OPDIVO 10 mg/mL concentrate for solution for infusion.
PRD2941372 · Product
- Active substance
- Nivolumab
- Substance synonyms
- BMS936558, ABP 206
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 360 mg/ml milligram(s)/millilitre
- Max total dose
- 360 mg/ml milligram(s)/millilitre
- Max treatment duration
- 14 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01FF01 — -
- Marketing authorisation
- EU/1/15/1014/001
- MA holder
- BRISTOL-MYERS SQUIBB PHARMA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
ANZ Breast Cancer Trials Group Limited
- Sponsor organisation
- ANZ Breast Cancer Trials Group Limited
- Address
- Level 4 175 Scott Street
- City
- Newcastle
- Postcode
- 2300
- Country
- Australia
Scientific contact point
- Organisation
- ANZ Breast Cancer Trials Group Limited
- Contact name
- Neon Trial Team
Public contact point
- Organisation
- ANZ Breast Cancer Trials Group Limited
- Contact name
- Neon Trial Team
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ended | 1 | 1 |
| Rest of world
New Zealand, Australia
|
— | 109 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2022-01-27 | 2025-07-18 | 2022-01-27 | 2022-04-01 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | BCT 1902 Neo-N Protocol Amendment 3_8 February 2023_Redacted | 3 |
| Recruitment arrangements (for publication) | placeholder doc_non-essential reason | 1 |
| Subject information and informed consent form (for publication) | Neo-N Main PICF- Version 1-1_11102021_ITA_clean | 1.1 |
| Subject information and informed consent form (for publication) | Neo-N Master Optional Tissue PICF - Version 1_31052021_ITA | 1 |
| Subject information and informed consent form (for publication) | Neo-N_Privacy ICF_ITA_V1-1_20211027_clean | 1.1 |
| Summary of Product Characteristics (SmPC) (for publication) | opdivo-epar-product-information_en | 1 |
| Synopsis of the protocol (for publication) | BCT 1902 Neo-N Protocol Synopsis_Protocol Version Amendment 3_8 February 2023 | 3 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-26 | Italy | Acceptable 2024-07-10
|
2024-07-22 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-09-20 | Italy | Acceptable 2024-07-10
|
2024-09-20 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-07-03 | Italy | Acceptable 2024-07-10
|
2025-07-03 |