ABCSG 47 / IMpassion030 Details *
A phase III, multicenter, randomized, open-label study comparing atezolizumab (anti PD-L1 antibody) in combination with adjuvant anthracycline/taxane-based chemotherapy versus chemotherapy alone in patients with operable triple-negative breast cancer
|Coordinating Investigator:||Günther Steger, Vienna|
|Sample size:||2300 (international)|
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To evaluate the efficacy of adjuvant atezolizumab + anthracycline/taxane-based chemotherapy compared with anthracycline/taxane-based chemotherapy alone in patients with TNBC
- To evaluate the efficacy of adjuvant atezolizumab + anthracycline/taxane-based chemotherapy compared with anthracycline/taxane-based chemotherapy alone
- To evaluate Patient Reported Outcomes of function and health related quality of life associated with atezolizumab + anthracycline/taxane-based chemotherapy compared with anthracycline/taxane-based chemotherapy alone, as measured by the functional and HRQoL scales of the EORTC QLQ-C30
- Signed Informed Consent Form (ICF)
- Ability to comply with protocol, in the investigator’s judgment
- Women or men aged ≥ 18 years at time of signing ICF
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Non-metastatic operable Stage II-IIII breast cancer
- Histologically documented TNBC (negative HER2, ER, and PgR status)
- Confirmed tumor PD-L1 evaluation as documented through central testing of arepresentative tumor tissue specimen
- Adequately excised: Patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy.
- Pathological tumor-node-metastasis staging (Union for International Cancer Control/American Joint Committee on Cancer [UICC/AJCC], 8th edition): Patient must have had sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) for evaluation of pathologic nodal status.
- Patients with synchronous bilateral invasive disease are eligible only if all bilateral invasive lesions are histologically confirmed as triple negative by central lab and have completed adequate pathological tumor-node metastasis staging bilaterally as described above.
- No more than 8 weeks (56 days) may elapse between definitive breast surgery (or the last surgery with curative intent if additional resection is required for breast cancer) and randomization.
- Baseline LVEF ≥ 53% measured by ECHO (preferred) or MUGA scans
Baseline LVEF to be conducted within 28 days prior to randomization.
- Adequate hematologic and end-organ function
- Negative HIV test at screening
- Negative hepatitis B surface antigen (HBsAg) test at screening
- Negative total hepatitis B core antibody (HBcAb) test at screening, or positive totalHBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCVantibody test followed by a negative HCV RNA test at screening
- Representative formalin-fixed, paraffin embedded (FFPE) tumor specimen from surgical resection in paraffin blocks (preferred) or at least 25 unstained slides, withan associated pathology report documenting locally assessed ER, PgR, and HER2 negativity.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm,
- Women who are not postmenopausal (> 12 months of nontherapy-induced amenorrhea) and have not undergone a sterilization procedure must have anegative serum pregnancy test result within 14 days prior to initiation of study drug.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of PRO questionnaires
- Prior history of invasive breast cancer
- Any T4 tumor as defined by tumor-node metastasis classification in UICC/AJCC, 8th edition, including inflammatory breast cancer
- For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment (e.g., neoadjuvant or adjuvant),
- Previous therapy with anthracyclines or taxanes for any malignancy
- History of DCIS and/or LCIS that was treated with any form of systemic, hormonal therapy, or RT to the ipsilateral breast where invasive cancer subsequently developed
- Patients who had their DCIS/LCIS treated only with surgery and/or contralateral
- DCIS treated with RT are allowed to enter the study.
- Contraindication to RT when adjuvant RT is clinically indicated
- Cardiopulmonary dysfunction prior to randomization
- Prior malignancies within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (i.e., adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer)
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
- Known allergy or hypersensitivity to any component of the atezolizumab formulation
- Known allergy or hypersensitivity to any component of the paclitaxel (e.g., polyoxyl 35 castor oil), cyclophosphamide, or doxorubicin/epirubicin formulations
- Known allergy or hypersensitivity to G-CSF or GM-CSF formulations
- Active or history of autoimmune disease or immune deficiency
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of activepneumonitis on screening chest computed tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Current treatment with anti-viral therapy for HBV
- Urinary outflow obstruction
- Active tuberculosis
- Severe infections 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
- Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during study treatment
- Prior allogeneic stem cell or solid organ transplant
- Administration of a live attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study or within 5 months after the last dose of atezolizumab
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
- Prior treatment with CD137 agonists or immune checkpointblockade therapies, including anti-CD40, antiCTLA-4, antiPD-1, and antiPD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents (including, but not limited to, interferons, interleukin-2) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to initiation of study treatment
- Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor [anti-TNF] alpha agents) within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medication during the study
- Pregnant or lactating, or intending to become pregnant during the study
- Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease
- Under any legal protection (tutorship/curatorship).
* studyinformation based on protocol version 6.0