Breast CancerPhase 2BIS-ProgramNCT05180006
Impact of Neoadjuvant Immunotherapy in Early Stage Breast Cancer Before Standard Therapy
A Phase 2 study testing Atezolizumab Injection, Bevacizumab and Pertuzumab in people with Breast Cancer, run by Gustave Roussy, Cancer Campus, Grand Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Atezolizumab Injection, Bevacizumab and Pertuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteFrance
- Study dates
- 24 Feb 2022to 17 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Bilirubin ≤ 1.5 x ULN, AST or ALT < 3 x ULN, ALP < 2.5 x ULN (patients with known Gilbert disease who have serum bilirubin level ≤ 3 × the institutional ULN may be enrolled)
- For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- Patients of child-bearing potential are eligible, provided they have a negative serum β-HCG pregnancy test within 2 weeks or urine pregnancy test within 48 hours prior to the first dose of study treatment, and agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, 28 days after the last dose of ipatasertib and 7 months after the last dose of pertuzumab and/or trastuzumab.
- A woman is considered of childbearing potential following menarche and until becoming post-menopausal (≥ 12 months of non-therapy-induced amenorrhea) unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral oophorectomy and bilateral salpingectomy.
- Sexually active women of childbearing potential must agree to use a highly effective method of contraception supplemented by a barrier method, or to abstain from sexual activity during the study and for at least 5 months after discontinuation of atezolizumab treatment, 6 months after the last dose of bevacizumab, 28 days after the last dose of ipatasertib and 7 months after the last dose of pertuzumab and/or trastuzumab. Female subjects should also refrain from breastfeeding throughout this period.
- A highly effective birth control method is a one, which can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include: combined (estrogen and progestogen containing) hormonal contraception; progestogen-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence during the entire period of risk associated with study treatment. To prevent the risk of interaction between the study drug and hormonal contraceptives, hormonal contraceptives should be supplemented with a barrier method (preferably male condom). Following methods are considered as unacceptable methods (non-exhaustive list): periodic abstinence (calendar, symptothermal, post-ovulation methods) and withdrawal (coitus interruptus).
- Sexually actives males patients must agree to use condom during the study and for at least 5 months after discontinuation of atezolizumab treatment, 6 months after the last dose of bevacizumab, 28 days after the last dose of ipatasertib and 7 months after the last dose of pertuzumab and/or trastuzumab. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception for the same duration.
- Patients must be affiliated to a social security system or beneficiary of the same.
Who cannot join
- Patients who meet any of the following exclusion criteria will not be eligible for this study.
- 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
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- 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
- History of idio pathic pulmonary fibrosis (including pneumonitis or interstitial lung disease), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis (history of radiation pneumonitis in the radiation field (fibrosis) is permitted).
- Patients who underwent major surgery within 28 days prior to inclusion or until the surgical wound is fully healed
- History of HIV infection
- Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
- Patients with a history cirrhosis
- Active tuberculosis
- Current treatment with anti-viral therapy for HBV
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including antiCTLA-4, antiPD-1, and antiPD-L1 therapeutic antibodies
- Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol
- Participation in another clinical study with an investigational product during the last 28 days and while on study treatment
- Currently known to have a history or ongoing serious retinopathy and/or history of retinal vein occlusion
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation or to any component of the other drugs on the study
- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
- Significant cardiovascular disease, such as:
- History of myocardial infarction, acute coronary syndromes or coronary angioplasty/stenting/bypass grafting within the past 6 months,
- Congestive Heart Failure (CHF) NYHA class III or IV or history of CHF NYHA class III or IV, unless an echocardiogram or multi-gated acquisition scan performed within 3 months day 1 reveals a left ventricular ejection fraction ≥ 50%55%
- Uncontrolled hypertension defined by systolic pressure > 150 and/or diastolic pressure > 110 mmHg, with or without anti-hypertensive medication. Patients with initial blood pressure elevations are eligible if initiation or adjustment of anti-hypertensive medication lowers blood pressure to meet entry criteria
- History of stroke or transient ischemic attack within 6 months prior to randomisation
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomisation
- History of haemoptysis (> 1/2 teaspoon of bright red blood per episode) or other serious haemorrhage or at risk of bleeding (gastrointestinal history of bleeds, gastrointestinal ulcers etc.) within 1 month prior to randomization
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.
- Pregnant or breastfeeding women
- Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent.
- For the TNBC cohort (exclusion criteria in relation to bevacizumab):
- Uncontrolled hypertension defined by systolic pressure > 150 and/or diastolic pressure > 110 mmHg, with or without anti-hypertensive medication. Patients with initial blood pressure elevations are eligible if initiation or adjustment of anti-hypertensive medication lowers blood pressure to meet entry criteria
- Currently known to have a history or ongoing serous retinopathy and/or history of retinal vein occlusion
- History of stroke or transient ischemic attack within 6 months prior to randomization
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization
- History of haemoptysis (> 1/2 teaspoon of bright red blood per episode) or other serious haemorrhage or at risk of bleeding (gastrointestinal history of bleeds, gastrointestinal ulcers etc.) within 1 month prior to randomization
- History of active inflammatory bowel disease (e.g. Crohn's disease and ulcerative colitis) or active bowel inflammation ( e.g. diverticulitis)
- Grade ≥ 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
- Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
- Known clinically significant history of liver disease consistent with Child Pugh Class B or C, including active viral or other hepatitis (e.g., positive for hepatitis B surface antigen [HBsAg] or hepatitis C virus [HCV] antibody at screening), current drug or alcohol abuse, or cirrhosis
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
Read the detailed description
Cohort 1 In TNBC patients t will be composed of 4 open-label, randomized arms:
Arm 1A: atezolizumab alone, administered as one single IV infusion on day -15 +/- 48 h Arm 1B: atezolizumab and bevacizumab as one single IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of the standard of care neoadjuvant systemic treatment.
Cohort 2 in HER2-positive patients will be composed of 2 arms:
Arm 2A: pertuzumab for one IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of the standard of care neoadjuvant systemic treatment.
Arm 2B: 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 the standard of care neoadjuvant systemic treatment.
- Conditions
- Breast Cancer
- Being tested
- Atezolizumab Injection, Bevacizumab, Pertuzumab, Trastuzumab
- Keywords
- triple-negative breast cancer, HER2+ breast cancer, non-metastatic breast cancer, immunotherapy, atezolizumab, ipatasertib, bevacizumab, trastuzumab, pertuzumab, GzmB+, CD8+
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atezolizumab InjectionDrug
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.).
BevacizumabDrug
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.
PertuzumabDrug
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.
TrastuzumabDrug
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Atezolizumab Injection; Drug: Pertuzumab; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to post-treatment (14 days) window.
Secondary outcomes (7)
Clinical response after experimental therapy
Clinical response after experimental therapy, defined as a > 30% decrease in tumour diameter from baseline breast ultrasound based on investigator assessment
Measured: From baseline to post-treatment (14 days) window.
pCR
pCR defined as the absence of any residual invasive cancer based on histological evaluation of the resected specimen during definitive breast cancer surgery.
Measured: From baseline to post-treatment (14 days) window.
Changes in CD8+ expression (Translational Study)
Changes in CD8+ expression from baseline (pre-study) to end of study-treatment biopsies
Measured: From baseline to post-treatment (14 days) window.
Changes in PD-L1 expression (Translational Study)
Changes in PD-L1 expression from baseline (pre-study) to end of study-treatment biopsies
Measured: From baseline to post-treatment (14 days) window.
Changes in % of Ki67 (Translational Study)
Changes in % of Ki67 from baseline (pre-study) to end of study-treatment biopsies
Measured: From baseline to post-treatment (14 days) window.
Changes in immune infiltrates (Translational Study)
Changes from baseline tumour tissue to end of treatment in immune infiltrates.
Measured: From baseline to post-treatment (14 days) window.
Changes in immune-related gene expression (Translational Study)
Changes from baseline tumour tissue to end of treatment in immune-related gene expression
Measured: From baseline to post-treatment (14 days) window.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2022
- Study start24 Feb 2022
- Primary completion17 Dec 2024
- Study completion17 Dec 2024
Why it stopped: Abandon of the partner, ROCHE
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Gustave Roussy, Cancer Campus, Grand ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Joana Mourato Ribeiro, Dr, Study director, Gustave Roussy, Cancer Campus, Grand Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05180006
- Sponsor's protocol ID
- 2020-004696-41
- Other IDs
- 2020/3130
- Acronym
- BIS-Program
- Status last verified
- Nov 2025
- First submitted
- 17 Dec 2021
- Last updated
- 1 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Neoadjuvant Immunotherapy in Early Stage Breast Cancer Before Standard Therapy
- ClinicalTrials.gov ID
- NCT05180006
- Acronym / sponsor ID
- BIS-Program / 2020-004696-41
- Conditions
- Breast Cancer
- Keywords
- triple-negative breast cancer, HER2+ breast cancer, non-metastatic breast cancer, immunotherapy, atezolizumab, ipatasertib, bevacizumab, trastuzumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Abandon of the partner, ROCHE
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand ParisUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- 24 Feb 2022 (actual)
- Primary completion
- 17 Dec 2024 (actual)
- Study completion
- 17 Dec 2024 (actual)
- First posted
- 6 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Cohort 1 In TNBC patients t will be composed of 4 open-label, randomized arms:
Arm 1A: atezolizumab alone, administered as one single IV infusion on day -15 +/- 48 h Arm 1B: atezolizumab and bevacizumab as one single IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of the standard of care neoadjuvant systemic treatment.
Cohort 2 in HER2-positive patients will be composed of 2 arms:
Arm 2A: pertuzumab for one IV infusion on day -15 +/- 48 h (D1) prior to the date of surgery or the start of the standard of care neoadjuvant systemic treatment.
Arm 2B: 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 the standard of care neoadjuvant systemic treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Arm 1A: Atezolizumab, in TNBC patients (cohort 1) | Active comparator | Drug: Atezolizumab Injectionatezolizumab 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. |
| Arm 1B: Atezolizumab + Bevacizumab, in TNBC patients (cohort 1) | Experimental | Drug: Atezolizumab Injection, Drug: Bevacizumabatezolizumab 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. |
| Arm 2A: Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2) | Active comparator | Drug: Pertuzumab, Drug: Trastuzumabtrastuzumab + 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. |
| Arm 2B: Atezolizumab + Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2) | Experimental | Drug: Atezolizumab Injection, Drug: Pertuzumab, Drug: Trastuzumabatezolizumab 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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
Key exclusion criteria (51 listed)
- Patients who meet any of the following exclusion criteria will not be eligible for this study.
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atezolizumab InjectionPatients 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.). | Drug | 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) |
| BevacizumabPatients 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. | Drug | Arm 1B: Atezolizumab + Bevacizumab, in TNBC patients (cohort 1) |
| PertuzumabPatients 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. | Drug | Arm 2A: Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2), Arm 2B: Atezolizumab + Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2) |
| TrastuzumabPatients 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. | Drug | Arm 2A: Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2), Arm 2B: Atezolizumab + Trastuzumab + Pertuzumab, in HER2+ patients (cohort 2) |
Primary outcome
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.
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.
7 secondary outcomes
Clinical response after experimental therapy
Time frame: From baseline to post-treatment (14 days) window.
pCR
Time frame: From baseline to post-treatment (14 days) window.
Changes in CD8+ expression (Translational Study)
Time frame: From baseline to post-treatment (14 days) window.
Changes in PD-L1 expression (Translational Study)
Time frame: From baseline to post-treatment (14 days) window.
Changes in % of Ki67 (Translational Study)
Time frame: From baseline to post-treatment (14 days) window.
Changes in immune infiltrates (Translational Study)
Time frame: From baseline to post-treatment (14 days) window.
Changes in immune-related gene expression (Translational Study)
Time frame: From baseline to post-treatment (14 days) window.
Results and safety
The study was stopped early (reason given: Abandon of the partner, ROCHE). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joana Mourato Ribeiro, Dr study director
Gustave Roussy, Cancer Campus, Grand Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Atezolizumab Injection, Bevacizumab and Pertuzumab in people with Breast Cancer, run by Gustave Roussy, Cancer Campus, Grand Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 51 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Abandon of the partner, ROCHE). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2025.