Pembrolizumab and Chemotherapy Treatment or no Treatment Guided by the Level of TILs in Resected Early-stage TNBC

NCT06078384 | Recruiting Phase 2 DMC

• 2 other identifiers: UC-BCG-22132023-504620-26-00
• Study Type: interventional
• Target: 354
• Locations: 2 countries
• Sites: 44

Brief Summary

Triple-negative breast cancer (TNBC) is a group of tumors that occurs mainly in young, premenopausal women and accounts for 10-20% of breast cancers. Over the past decade, the incidence of women diagnosed with early-stage TNBC has significantly increased due to the widespread use of screening mammography. Treatment of patients with localized TNBC mainly involves surgery and (neo)adjuvant chemotherapy with or without radiotherapy. However, the benefit of chemotherapy may be controversial in patients with early-stage TNBC defined by small size and absence of lymph node involvement, and with significant tumor lymphocyte infiltration. The ETNA study is a phase II trial designed to evaluate a chemotherapy de-escalation strategy in patients with TNBC T1b/c N0M0 and stromal TILs (sTILs) ≥ 30%. ETNA comprises two cohorts defined according to the level of TILs and the age of patients. Patients aged \> 40 years with 30% ≤ sTILs \< 50% and those aged ≤ 40 years with 30% ≤ sTILs \< 75% will be included in the cohort 1 and will receive adjuvant pembrolizumab 200 mg every three weeks for 9 cycles and Paclitaxel 80 mg/m² weekly for 12 cycles. Patients aged \> 40 years with sTILs ≥ 50% and those aged ≤ 40 years with sTILs ≥ 75% will be included in cohort 2 and will not receive adjuvant treatment, they will undergo standard surveillance every six months.

Conditions

Triple-negative Breast Cancer

Keywords

Breast cancer; De-escalation; Immunotherapy; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Distant disease-free survival (DDFS)

  Distant disease-free survival is defined as the delay between date of inclusion and distant tumor relapse, second cancer, or death from any cause, whichever occurs first.

  5 year

Secondary Outcomes (8)

• Invasive disease-free survival (IDFS)

  From inclusion up to 5 year

• Distant recurrence-free survival (DRFS)

  From inclusion up to 5 year

• Overall survival (OS)

  From inclusion to death from any cause, up to 5 year

• Incidence of Adverse Events

  Throughout study completion, up to 5 year

• Quality of life questionnaire - Core 30 (QLQ-C30)

  At baseline, every 3 weeks for 6 months then every 6 months up to 5 years

Study Arms (2)

Cohort 1-Pembrolizumab plus Paclitaxel

EXPERIMENTAL

Pembrolizumab will be administered at a fixed dose of 200 mg every 3 weeks (Q3W), with a total of 9 cycles and Paclitaxel 80 mg/m² weekly for 12 cycles

Drug: Pembrolizumab 25 mg/ml; Drug: Paclitaxel injection

Cohort 2-Observation

NO INTERVENTION

No treatment will be administered, patients will undergo standard surveillance every 6 months according to local practice.

Interventions

Pembrolizumab 25 mg/ml DRUG

Pembrolizumab drug product is a sterile-filtered liquid and is aseptically filled into single-use vials. The vials contain 4 mL of sterile solution for IV infusion.

Also known as: keytruda

Cohort 1-Pembrolizumab plus Paclitaxel

Paclitaxel injection DRUG

Injectable solution for IV administration. Dose of 80 mg/m² weekly.

Also known as: Taxol

Cohort 1-Pembrolizumab plus Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Understand, sign, and date the written informed consent form prior to any protocol- specific procedures performed,
• Men and women aged ≥ 18 years,
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1,
• Histologically confirmed and radically removed pT1b/c N0M0 TNBC as defined according to AJCC TNM stage-8th version,
• Histologically documented TNBC (negative HER2, ER, and PgR status). HER2 negativity is defined by local laboratory assessment using in situ hybridization and immunohistochemistry assays as per ASCO/CAP criteria and ER/PgR negativity is defined by local laboratory assessment \< 10% using immunohistochemistry assays,
• Bilateral and/or multifocal primary tumor is allowed and the tumor with the most advanced T stage should be used to asses for eligibility. If multifocal tumor, a pathologic confirmation of TNBC is required for each focus,
• Adequately excised breast cancer: subjects must have undergone either breast- conserving surgery or mastectomy/nipple- or skin-sparing mastectomy.
• For subjects who undergo breast-conserving surgery, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. Reresections to ensure no ink on tumor margins are allowed. Subjects with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection.
• For subjects who undergo mastectomy/nipple- or skin-sparing mastectomy, margins must be free of gross residual tumor. It is recommended that subjects should have a negative microscopic margin in accordance with local pathology protocol,
• 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),
• 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,
• Centrally assessed TILs score from surgical formalin-fixed paraffin embedded (FFPE) tumor sample, using an H\&E stained diagnostic digital slide, according to the most recent International TILs Working Group guidelines,
• Cohort 1 will include patients aged \> 40 years with 30% ≤ sTILs \< 50% and those aged
• years with 30% ≤ sTILs \< 75%

You may not qualify if:

• History of invasive malignancy ≤ 3 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer,
• Having received prior chemotherapy or targeted therapy within the past 12 months,
• 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,
• 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),
• Subjects who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study
• The use of inhaled corticosteroids and mineralocorticoids is allowed,
• 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 exacerbations requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or oral corticosteroids occurred within the previous 12 months,
• Has a known history of Human Immunodeficiency Virus (HIV),
• Prior allogeneic stem cell or solid organ transplant,
• Has a known history of active Bacillus Tuberculosis,
• Patients with any other disease or illness which requires hospitalisation or is incompatible with the trial treatment are not eligible,
• 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,
• Person deprived of their liberty or under protective custody or guardianship,

Sponsors & Collaborators

• UNICANCER: lead
• MSD France: collaborator
• SOLTI Breast Cancer Research Group: collaborator
• Gustave Roussy, Cancer Campus, Grand Paris: collaborator
• Vall Hebron Insitut Recerca: collaborator

Study Sites (44)

CHU Amiens Picardie_Site Sud

Amiens, 80054, France

RECRUITING

Institut Sainte Catherine

Avignon, 84918, France

RECRUITING

Centre Hospitalier de la Côte Basque

Bayonne, 64109, France

RECRUITING

Institut Bergonié

Bordeaux, 33000, France

NOT YET RECRUITING

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, 33077, France

RECRUITING

Centre François Baclesse

Caen, 14000, France

RECRUITING

Pôle Santé Republique

Clermont-Ferrand, 63000, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63011, France

RECRUITING

Centre Georges-François Leclerc

Dijon, 21000, France

NOT YET RECRUITING

Hôpital Franco-Britannique-Fondation Cognacq-Jay

Levallois-Perret, 92300, France

NOT YET RECRUITING

CHU de Limoges

Limoges, 87042, France

RECRUITING

Centre Léon Bérard

Lyon, 69008, France

RECRUITING

Hopital Privé Jean Mermoz

Lyon, 69008, France

RECRUITING

Institut Paoli-Calmettes

Marseille, 13009, France

RECRUITING

Institut régional du Cancer de Montpellier

Montpellier, 34298, France

NOT YET RECRUITING

Hôpital privé du confluent

Nantes, 44200, France

RECRUITING

Centre Antoine Lacassagne

Nice, 61000, France

RECRUITING

CHU de Nîmes

Nîmes, 30029, France

RECRUITING

Centre Hospitalier de Pau

Pau, 64046, France

RECRUITING

Hôpital Privé des côtes d'Armor

Plérin, 22190, France

NOT YET RECRUITING

Hôpital NOVO

Pontoise, 95300, France

RECRUITING

Centre Hospitalier de Cornouaille

Quimper, 29107, France

RECRUITING

Clinique La Croix du Sud

Quint-Fonsegrives, 31130, France

WITHDRAWN

Institut Godinot

Reims, 51100, France

RECRUITING

Centre Eugène Marquis

Rennes, 35000, France

RECRUITING

CHU de Saint Etienne

Saint-Etienne, 42055, France

RECRUITING

Institut Claudius Regaud

Toulouse, 31059, France

RECRUITING

CHU Bretonneau

Tours, 37000, France

RECRUITING

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54519, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Hospital General Universitario Dr.Balmis

Alicante, Spain

NOT YET RECRUITING

Ico Badalona

Badalona, 08916, Spain

NOT YET RECRUITING

Hospital Vall D'Hebrón

Barcelona, 08035, Spain

NOT YET RECRUITING

Hospital Clinico Universitario Virgen de La Arrixaca

El Palmar, 30120, Spain

NOT YET RECRUITING

Hospital Universitario Clinico San Cecilio

Granada, 18016, Spain

NOT YET RECRUITING

Ico Hospitalet

L'Hospitalet de Llobregat, 08908, Spain

RECRUITING

Complejo Asistencial Universitario de Leon

León, 24071, Spain

NOT YET RECRUITING

Hu Arnau de Vilanova Lleida

Lleida, 25198, Spain

NOT YET RECRUITING

Hospital Ramon Y Cajal

Madrid, 28034, Spain

NOT YET RECRUITING

Hospital 12 de Octubre

Madrid, 28041, Spain

NOT YET RECRUITING

Hospital Universitari Son Espases

Palma de Mallorca, 07120, Spain

NOT YET RECRUITING

Hospital Sant Joan de Reus

Reus, 43204, Spain

NOT YET RECRUITING

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

NOT YET RECRUITING

Hospital Clínico Valencia

Valencia, 46010, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

pembrolizumab; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Elie Rassy, MD

  Gustave Roussy, Villejuif, France

  PRINCIPAL INVESTIGATOR

• Barbara Pistilli, MD

  Gustave Roussy, Villejuif, France

  PRINCIPAL INVESTIGATOR

• Mafalda Oliveira, MD

  HOSPITAL VALL D'HEBRÓN, Barcelona, Spain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Telma ROQUE, PhD

CONTACT

+33 (0) 1 80 50 12 92; etna@unicancer.fr

Sylvie Mijonnet

CONTACT

s-mijonnet@unicancer.fr

Study Design

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

Model Details: Cohort of patients with T1b/c N0 M0 TNBC aged \> 40 years with 30% ≤ sTILs \< 50% and those aged ≤ 40 years with 30% ≤ sTILs \< 75%: Pembrolizumab will be administered at a fixed dose of 200 mg every 3 weeks (Q3W), with a total of 9 cycles and Paclitaxel 80 mg/m² weekly for 12 cycles at adjuvant phase of the treatment; Cohort of patients with T1b/c N0 M0 TNBC aged \> 40 years and sTILs ≥ 50% and those aged ≤ 40 years with sTILs ≥ 75%: No treatment will be administered. These patients will undergo standard surveillance every 6 months according to local practice.

Study Record Dates

• First Submitted: October 5, 2023
• First Posted: October 11, 2023
• Study Start: December 27, 2024
• Primary Completion (Estimated): January 1, 2032
• Study Completion (Estimated): January 1, 2032
• Last Updated: November 17, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (14); FR (30)