Impact of Neoadjuvant Immunotherapy in Early Stage Breast Cancer Before Standard Therapy

Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Study ID
NCT05180006
Phase
PHASE2
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Atezolizumab Injection — DRUG
    Patients randomized to an atezolizumab arm will receive atezolizumab 840 mg IV on D1 (15 days +/- 48 h before the surgery date or the biopsy prior to the start of standard of care neoadjuvant systemic treatment.).
  • Bevacizumab — DRUG
    Patients in the atezolizumab plus bevacizumab arm will receive a unique dose of bevacizumab as 10 mg/kg administered by IV infusion over 60 mins on day 1 cycle 1 (15 days before surgery +/- 48 h), the same day as atezolizumab.
  • Pertuzumab — DRUG
    Patients in the atezolizumab plus trastuzumab plus pertuzumab arm will receive single doses of pertuzumab on day 1 administered IV. Pertuzumab will be administered IV at a loading dose of 840 mg.
  • Trastuzumab — DRUG
    Patients in the atezolizumab plus trastuzumab plus pertuzumab arm will receive single doses of Trastuzumab on day 1 administered IV. Trastuzumab will be given at a loading dose of 8 mg/kg.

Study Details

The aim of this study is to determine, using immunohistochemistry (IHC) on biopsies and surgically removed tumor if short-treatment immunotherapy with atezolizumab monotherapy or in combination with other biologic agents (ipatasertib / Bevacizumab / Trastuzumab / Pertuzumab) is associated with increased levels of activated GzmB+ CD8+ T cells from baseline to post treatment sample. Moreover, from baseline to post treatment sample, evolution of others biomarkers will be studied : GzmB/CD8, CD8/FoxP3, CD8/CD68 in IHC, cell proliferation, PD-L1, MHC-I, change in gene expression (RNA-Seq). Tjis study aim also to assess the safety and tolerability of study treatments in this population and to determine the effect of short-term immunotherapy treatment in pCR at surgery. Patients will undergo tumor biopsies at screening and 15 days after the beginning of treatment (if they start neoadjuvant chemotherapy) / at surgery, in order to evaluate in IHC evolution of activated GzmB+ CD8+ T cells and evaluate other markers It targets 2 different cohorts: newly diagnosed, non-metastatic early-stage triple-negative (TNBC) or HER2+ breast cancer. TNBC cohort is composed of 2 open-label, randomized arms, HER2+ of 2 arms. A maximum of 185 patients will be included in the trial Tumor evaluation will be performed by clinical examination and Breast echography at baseline and end of treatment visit. The safety of the product will be assessed at each cycle, through complete clinical exams, biological tests and through the collection of ongoing toxicities or adverse events.

Key Dates

Start date
Feb 24, 2022
Status verified
Nov 2025
Primary completion
Dec 17, 2024
Completion
Dec 17, 2024

Study Design

Enrollment
33 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Arm 1A: Atezolizumab, in TNBC patients (cohort 1)
    atezolizumab alone, administered as one single IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of standard of care neoadjuvant systemic treatment.
  • Experimental: Arm 1B: Atezolizumab + Bevacizumab, in TNBC patients (cohort 1)
    atezolizumab and bevacizumab as one single IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of standard of care neoadjuvant systemic treatment.
  • Active Comparator: Arm 2A: Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2)
    trastuzumab + pertuzumab for one IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of standard of care neoadjuvant systemic treatment.
  • Experimental: Arm 2B: Atezolizumab + Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2)
    atezolizumab as one single IV infusion in combination with trastuzumab + pertuzumab for one IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of standard of care neoadjuvant systemic treatment.

Primary Outcome Measure

Two-fold increase in GzmB+ CD8+ T cell levels from baseline to post-treatment window. [ Time Frame: From baseline to post-treatment (14 days) window. ]

Related Studies