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

NCT05180006 | Terminated Phase 2 DMC

• 2 other identifiers: 2020-004696-412020/3130
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Keywords

triple-negative breast cancer; HER2+ breast cancer; non-metastatic breast cancer; immunotherapy; atezolizumab; ipatasertib; bevacizumab; trastuzumab; pertuzumab; GzmB+; CD8+

Outcome Measures

Primary Outcomes (1)

• Two-fold increase in GzmB+ CD8+ T cell levels from baseline to post-treatment window.

  To determine, using immunohistochemistry (IHC) on biopsies and surgically removed tumor whether short-treatment immunotherapy with atezolizumab monotherapy or in combination with other biologic agents is associated with increased levels of activated GzmB+ CD8+ T cells from baseline to post treatment sample.

  From baseline to post-treatment (14 days) window.

Secondary Outcomes (7)

• Clinical response after experimental therapy

  From baseline to post-treatment (14 days) window.

• pCR

  From baseline to post-treatment (14 days) window.

• Changes in CD8+ expression (Translational Study)

  From baseline to post-treatment (14 days) window.

• Changes in PD-L1 expression (Translational Study)

  From baseline to post-treatment (14 days) window.

• Changes in % of Ki67 (Translational Study)

  From baseline to post-treatment (14 days) window.

Study Arms (4)

Arm 1A: Atezolizumab, in TNBC patients (cohort 1)

ACTIVE COMPARATOR

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.

Drug: Atezolizumab Injection

Arm 1B: Atezolizumab + Bevacizumab, in TNBC patients (cohort 1)

EXPERIMENTAL

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.

Drug: Atezolizumab Injection; Drug: Bevacizumab

Arm 2A: Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2)

ACTIVE COMPARATOR

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.

Drug: Pertuzumab; Drug: Trastuzumab

Arm 2B: Atezolizumab + Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2)

EXPERIMENTAL

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.

Drug: Atezolizumab Injection; Drug: Pertuzumab; Drug: Trastuzumab

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.).

Arm 1A: Atezolizumab, in TNBC patients (cohort 1); Arm 1B: Atezolizumab + Bevacizumab, in TNBC patients (cohort 1); Arm 2B: Atezolizumab + Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2)

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.

Arm 1B: Atezolizumab + Bevacizumab, in TNBC patients (cohort 1)

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.

Arm 2A: Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2); Arm 2B: Atezolizumab + Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2)

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.

Arm 2A: Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2); Arm 2B: Atezolizumab + Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2)

Eligibility Criteria

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

You may qualify if:

• Patient should understand, sign, and date the written informed consent form prior to any protocol-specific procedures performed. Patient should be able and willing to comply with study visits and procedures as per protocol.
• Female or male patients aged 18 years or older
• Eastern Cooperative Group (ECOG) Performance Status 0-1
• Histologically confirmed female breast cancer with no evidence of metastatic spread
• Candidate to surgery upfront or patients with an indication to standard of care neoadjuvant systemic treatment, assuming that systemic treatment starts after the completion of the pre-operative immunotherapy treatment, biopsies are undertaken before the start of the systemic treatment and the decision to administer neoadjuvant systemic treatment is made before randomization
• At least 11 mm in tumor size as determined by breast ultrasound
• ER, PR and HER2 will be locally assessed and defined as per the french national guidelines:
• For the TNBC cohort, ER≤10%, PR≤10% and HER2 not overexpressed/amplified
• For the HER2-positive cohort, presence of a HER2 overexpression and/or amplification as per ASCO/CAP guidelines
• Adequate haematologic and organ function defined by the following:
• ANC ≥ 1,500 cells/µl
• Platelet count ≥ 100,000/µl
• Haemoglobin ≥ 9.0 g/dL (90g/L)
• Serum albumin ≥ 2.5 g/dL
• Creatinine ≤ 1.5 x ULN

You may not qualify if:

• Evidence of metastatic breast cancer
• ER≥10% or PR≥10%and/or HER2+ (for the TNBC cohort) and HER2- (for the HER2+ cohort)
• Any systemic therapy (e.g, chemotherapy, targeted therapy, immune-therapy) or radiotherapy for current breast cancer disease before study entry
• Previous systemic treatment for other neoplasms within 1 year prior to randomization
• Active malignancy (except for non-melanoma skin cancer, or histologically confirmed complete excision of carcinoma in-situ) within the past 36 months prior to study entry
• Known intolerance to any of the study drugs or any of their excipients
• Patients with prior allogeneic stem cell or solid organ transplantation
• Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study or within 5 months after the last dose of atezolizumab
• Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate and thalidomide) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
• Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids as premedication for hypersensitivity reaction (e.g., CT scan premedication)) are eligible for the study after Medical Monitor approval has been obtained
• Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
• Patients who received intranasal, inhaled, topical or local steroid injections (e.g., intra articular injection)
• Active or history of autoimmune disease or immune deficiency, with the exception of history of treated autoimmune-related hypothyroidism and Type 1 diabetes mellitus on insulin regimen
• Symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Gustave Roussy

Villejuif, 94800, France

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

atezolizumab; Bevacizumab; pertuzumab; Trastuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Joana Mourato Ribeiro, Dr

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY DIRECTOR

Study Design

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

Model Details: The design of this study follows an adaptive, open, prospective randomized model : Cohort 1 TNBC patients: they will be randomized 1:1 to either atezolizumab alone administered as one single IV infusion on day -15 +/- 48h prior to the date of surgery or the start of the standard of care neoadjuvant systemic treatment, or atezolizumab and bevacizumab as one single IV infusion on day -15 +/- 48h prior to the date of surgery or the start of neoadjuvant treatment Cohort 2 in HER2-positive patients: they will be randomized 1:1 to either trastuzumab and pertuzumab for one IV infusion on day -15 +/- 48h prior to the surgery or the start of neoadjuvant treatment, or atezolizumab as one single IV infusion in combination with trastuzumab and pertuzumab for one IV infusion on day -15 +/- 48h prior to the surgery or the start of neoadjuvant treatment

Study Record Dates

• First Submitted: December 17, 2021
• First Posted: January 6, 2022
• Study Start: February 24, 2022
• Primary Completion: December 17, 2024
• Study Completion: December 17, 2024
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)