NCT06078384

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

Adjuvant Pembrolizumab and Chemotherapy or Surveillance in Early Triple Negative breAst Cancer With High Stromal Tumor-infiltrating Lymphocytes (TILs) Score

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 354 (estimated)
• Sponsor: UNICANCER · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

(Neo)adjuvant chemotherapy in breast cancer is associated to long-term persistent QoL deterioration in patients with early breast cancer, with a greater negative impact in patients that were premenopausal at diagnosis. Because triple negative breast cancer (TNBC), which accounts for 10-20% of breast cancers, presents a poorer prognosis as compared to the other subtypes, international guidelines endorse the use of adjuvant chemotherapy from TNBC tumors measuring \> 5 mm. Nevertheless, a number of retrospective studies have reported excellent prognosis for patients with small, lymph node-negative and high TILs TNBC, even without chemotherapy, with 5-year overall survival (OS) of 98%. Findings from multiple data sets consistently demonstrated that TILs represent a robust prognostic and predictive biomarker in early-stage TNBC, being now the first biological prognostic marker for TNBC included in several international guidelines for early-stage disease, such as 2019 St Gallen consensus conference and European Society for Medical Oncology (ESMO) Guidelines for early-stage breast cancer. In clinical practice, oncologists have taken different approaches in patients with stage I TNBC. While some have de-escalated anthracyclines, other did not held back on the standard chemotherapy options with anthracyclines, taxanes, and cyclophosphamide. Based on unpublished data from the TNBC pooled analysis with sTILs on 2211 patients not treated by systematic therapy, performed at Gustave Roussy, the 5-year distant disease free-survival (DDFS) is 87%, 91%, and 93% for those with stage I and sTILs ≥ 30%, 50%, and 75%, respectively. Given these compelling findings from historical observations, it is reasonable to anticipate that the absolute benefit of chemotherapy would be modest among these patients as their tumors generally exhibit a favorable prognosis, resulting in reduced benefits with the use of adjuvant chemotherapy. ETNA is a phase II, multicenter, biomarker-driven study that is designed to characterize the clinical course of patients with stage I TNBC and sTILs ≥ 30%. ETNA includes patients with stage I and sTILs ≥ 30% TNBC in 2 cohorts: * Cohort 1 will include patients age \> 40 years with 30% ≤ sTILs \< 50% and those aged ≤ 40 years with 30% ≤ sTILs \< 75%. Patients will receive 9 cycles of adjuvant pembrolizumab 200 mg every three weeks for 9 cycles and Paclitaxel 80 mg/m² weekly for 12 cycles. * Cohort 2 will include patients aged \> 40 years with sTILs ≥ 50% and those aged ≤ 40 years with sTILs ≥ 75% who will undergo standard surveillance (no adjuvant systemic treatments).

Conditions

• Triple-negative Breast Cancer

Interventions

Type	Name	Description
DRUG	Pembrolizumab 25 mg/ml	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.
DRUG	Paclitaxel injection	Injectable solution for IV administration. Dose of 80 mg/m² weekly.

Timeline

• Start date: 2024-12-27
• Primary completion: 2032-01-01
• Completion: 2032-01-01
• First posted: 2023-10-11
• Last updated: 2025-11-17

Locations

44 sites across 2 countries: France, Spain