Immunotherapy and chemotherapy treatment or no treatment guided by the level of tumour-infiltrating cells in resected early-stage triple-negative breast cancer (i.e. without hormone receptor or HER2 protein receptor)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer, Institut Gustave Roussy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 Nov 2024 → ongoing

Decision date (initial)

2024-05-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

PHRC 2022 · La ligue contre le cancer · Real Life Oncology Programme · Gustave Roussy

External identifiers

EU CT number

2023-504620-26-00

ClinicalTrials.gov

NCT06078384

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Cohort 1: to assess the 5-year investigator-assessed DDFS in patients with pT1b/cN0M0 TNBC among those aged > 40 years with 30% ≤ sTILs < 50% and those aged ≤ 40 years with 30% ≤ sTILs < 75% receiving adjuvant pembrolizumab plus paclitaxel.
Cohort 2: to estimate the 5-year investigator-assessed DDFS in patients with pT1b/cN0M0 TNBC among those aged > 40 years with sTILs ≥ 50% and those aged ≤ 40 years with sTILs ≥ 75% who will undergo standard surveillance (no adjuvant systemic treatments).

Secondary objectives 4

1. Efficacy : To determine the invasive-disease-free survival, distant recurrence-free survival and overall survival (cohorts 1 and 2 will be analysed independently)
2. Safety : Cohort 1: to determine the safety and tolerability of adjuvant pembrolizumab plus paclitaxel, assessed by Adverse Events as per common terminology criteria for adverse events of the National Cancer Institute v. 5.0.
3. Quality of life assessment : To determine short and long-term patient’s QoL, assessed through EORTC QLQ-C30, EORTC QLQ-BR23, EORTC QLQ-FA12 and Hospital anxiety and depression scale (HADS) – anxiety subscale in the two cohorts.
4. Pooled analysis : To perform a pooled analysis of survival outcomes in cohort 2 together with the similary EORTC OPTIMAL study and, if feasible, other further international studies evaluating adjuvant treatment optimization in patients with early TNBC and high TILs.

Conditions and MedDRA coding

Triple negative breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed
2. Men and women aged ≥ 18 years,
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1,
4. Histologically confirmed and radically removed pT1b/c N0M0 TNBC as defined according to AJCC TNM stage-8th version,
5. Adequately excised breast cancer: subjects must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy.
6. Have had sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) for evaluation of pathologic nodal status. Axillary nodal dissection(s) should yield a total of at least six nodes (including the axillary lymph nodes resected at the SLNB plus the lymph nodes collected at the axillary nodal dissection)
7. At least 4 weeks but no more than 12 weeks between definitive breast surgery (or the last surgery with curative intent if additional resection is required for breast cancer) and treatment initiation for cohort 1 and no more than 12 weeks for cohort 2,
8. Centrally assessed TILs rate from surgical FFPE tumor sample , using an H&E stained diagnostic digital slide, according to the most recent International TILs Working Group guidelines,
9. Women of childbearing potential have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication for cohort 1 and within 7 days of inclusion for cohort 2,
10. Women of childbearing potential must agree to use protocol-specified method(s) of contraception for 3 years after patient inclusion. Men subjects who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception during trial treatments and for at least 6 months after the last dose of trial treatments. Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year,
11. Patients affiliated to the social security system (or equivalent)- France only,
12. Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.
13. For cohort 1 : Left ventricular ejection fraction (LVEF) of ≥ 50% as assessed by echocardiogram or cardiac scintigraphy
14. For cohort 1 : Demonstrate adequate organ function within 7 days of inclusion

Exclusion criteria 24

1. History of invasive malignancy ≤ 3 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer
2. Having received prior chemotherapy or targeted therapy within the past 12 months
3. Has a prior history of DCIS and/or LCIS that was treated with any form of systemic, hormonal therapy, or radiotherapy to the ipsilateral breast; subjects who had their DCIS/LCIS treated only with surgery and/or contralateral DCIS treated with radiotherapy are allowed to enter the study
4. Having received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agents or with an agent directed to another co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137)
5. Treatment with systemic immunostimulatory agents (including, but not limited to, interferons, interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to inclusion
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive medications (including prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] alpha agents) within 7 days prior to inclusion
7. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment; subjects with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible if: Rash must covers <10% of body surface area & Disease is well controlled at baseline and requires only low-potency topical Corticosteroids and no acute exarcerbations requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or oral corticosteroids occurred within the previous 12 months
8. Has a known history of Human Immunodeficiency Virus (HIV),
9. Prior allogeneic stem cell or solid organ transplant,
10. Has a known history of active Bacillus Tuberculosis,
11. Patients with any other disease or illness which requires hospitalisation or is incompatible with the trial treatment are not eligible,
12. Pregnant women or breastfeeding or expecting to conceive within the projected duration of the study, from the inclusion visit until the end of the 3 years follow up. Men subjects who engage in heterosexual intercourse and refuse to use protocol-specified method(s) of contraception during trial treatments and for at least 6 months after the last dose of trial treatments,
13. Patients unable to comply with trial obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the trial,
14. Person deprived of their liberty or under protective custody or guardianship,
15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
16. For cohort 1 : Has cardiac dysfunction as defined by any of the following prior to inclusion: - History of NCI-CTCAE v5.0 Grade > 3 symptomatic congestive heart failure or New York Heart Association (NYHA) criteria Class II, - Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease, - Significant symptoms (≥ Grade 2) relating to left ventricular dysfunction or cardiac ischemia,
17. For cohort 1 : Has a known hypersensitivity (≥ Grade 3) to the components of the study therapy or its analogs,
18. For cohort 1 : Has received a live vaccine or live-attenuated vaccine within 30 days of the first dose of study treatment
19. For cohort 1 : Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection
20. For cohort 1 : Severe infections within 4 weeks prior to initiation of study treatment, including, hospitalization for complications of infection, bacteremia, or severe pneumonia,
21. For cohort 1 : Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment; subjects receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection) are eligible,
22. For cohort 1 : Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during study treatment,
23. For cohort 1 : Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has a current pneumonitis/interstitial lung disease
24. For cohort 1 : Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is DDFS in cohort 1 and in cohort 2. DDFS is defined from the time from inclusion to the following events whichever comes first: distant recurrence of breast cancer, second primary non breast cancer, and death from any cause.

Secondary endpoints 6

1. Efficacy - IDFS is defined from the time from inclusion to the following events whichever comes first : Ipsilateral invasive breast tumor recurrence; Regional invasive breast tumor recurrence; Distance recurrence; Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause; Second primary malignancy.
2. Efficacy - DRFS is defined from the time from inclusion to the following events whichever comes first: distant recurrence of breast cancer, and death from any cause.
3. Efficacy - OS is defined as the time from inclusion to date of death from any cause.
4. Safety - Cohort 1: Safety and tolerability of pembrolizumab plus paclitaxel will be measured, every 3 weeks while on treatment and thereafter every 6 months for 5 years from study entry
5. Quality of life assessment - QoL domains will be assessed using: EORTC QLQ-C30, EORTC QLQ-B23, EORTC QLQ-FA12, and HADS – anxiety subscale.
6. Exploratory endpoints - Comprehensive exploratory analysis will be performed on tumor tissue (initial biopsy, surgery and recurrence biopsy) and blood samples.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Institut Gustave Roussy

Sponsor organisation

Institut Gustave Roussy

Address

114 Rue Edouard Vaillant

City

Villejuif

Postcode

94800

Country

France

Sponsor responsibilities

Article 77 compliance

Unicancer

Contact point sponsor

Unicancer

Article 77 implementation

Unicancer

Locations

2 EU/EEA countries · 45 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 8 files

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

Application history

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