Study to Compare a Mono Atezolizumab Window Followed by a... | NCT04770272

Name	Class
Roche Pharma AG	INDUSTRY
Phaon Scientific GmbH	UNKNOWN
University Hospital, Essen	OTHER
University Hospital Erlangen

Description Module

Detailed Description

This is a randomized, open-label, adaptive, two arm, multicenter phase II trial that enrolled female and male patients with primary TNBC (defined as ER/PR < 10% and HER2-negative) with tumor stages cT1c - cT4d (cN0 and cN+). Patients are randomized to Arm A and B. Randomization is stratified by PD-L1 expression on immune cells (IC-status) and anatomic tumor stage (according to the AJCC 8th edition Anatomic Stage Groups I, II andIII). PD-L1 status is determined by central pathology using the VENTANA PD-L1 (SP142) assay and is defined by PD-L1 IC expression.

Patients in Arm A receive a 2-week monotherapy of Atezolizumab 840 mg q2w prior to initiation of a 12-week neoadjuvant CTX therapy with Paclitaxel 80 mg/m2 i.v. q1w x 12 doses + Carboplatin AUC of 2 i.v. q1w x 12 doses + Atezolizumab 1200 mg day 1 every 3 weeks for 4 doses followed by Epirubicin 90 mg/m2 + Cyclophosphamide 600 mg/m2, both q3w for 4 cycles + Atezolizumab 1200 mg day 1 every 3 weeks for 4 doses.

Patients in Arm B are treated with a neoadjuvant 12-week regimen of Paclitaxel 80 mg/m² i.v. q1w x 12 doses + Carboplatin AUC of 2 i.v. q1w x 12 doses + Atezolizumab 1200 mg day 1 every 3 weeks for 4 doses without a monotherapy window. This is followed by Epirubicin 90 mg/m² + Cyclophosphamide 600 mg/m2, both q3w for 4 cycles + Atezolizumab 1200 mg day 1 every 3 weeks for 4 doses.

Patients in both arms undergo surgery after 29 - 30 weeks therapy in total for Arm A and 27 - 28 weeks therapy in total for Arm B (3 - 4 weeks after last dose of neoadjuvant therapy).

Safety and toxicities under therapy are supervised via regular DSMB meetings. After surgery, patients are treated according to the local SoC therapy for TNBC and followed-up for 24 months.

Label	Type	Description	Intervention Names
Arm A	Experimental	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles.	Drug: Atezolizumab 840 MG in 14 ML Injection Drug: Atezolizumab 1200 MG in 20 ML Injection Drug: Carboplatin Drug: Paclitaxel Drug: Epirubicin Drug: Cyclophosphamide Procedure: Biopsy Arm A Procedure: Surgery
Arm B	Active Comparator	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles.	Drug: Atezolizumab 1200 MG in 20 ML Injection Drug: Carboplatin Drug: Paclitaxel Drug: Epirubicin Drug: Cyclophosphamide Procedure: Biopsy Arm B Procedure: Surgery

Name	Type	Description	Arm Group Labels	Other Names
Atezolizumab 840 MG in 14 ML Injection	Drug	840 mg Day 1 for two weeks	Arm A

Measure	Description	Time Frame
Pathological Complete Response (ypT0/is, ypN0)	Pathological Complete Response defined as no residual invasive tumor cells in the breast and in the lymph nodes (ypT0/is, ypN0).	after 29-30 weeks in Arm A and after 27-28 weeks in Arm B.

Measure	Description	Time Frame
Number of Adverse Events by Grade	Safety (incidence, relationship, seriousness, and severity of all AEs, SAEs, AESIs coded by medical dictionary for regulatory activities (MedDRA), summarized by Preferred Term and System Organ Class and graded according to common terminology criteria of adverse events (CTCAE V5.0)	from date of randomization up to 24 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Female and male patients, age at diagnosis 18 years and above
Written informed consent prior to admission to this study
Histologically confirmed unilateral primary invasive carcinoma of the breast
Clinical T1c - T4d
Stage N0-N3 until 21 patients (5%) with stage N3 are randomized, thereafter N0-N2
Triple negative breast cancer defined by and confirmed by central pathology:
- ER negative (<10% positive cells in IHC) and PR negative (<10% positive cells on IHC)
- HER2 negative breast cancer:
  - Either defined by IHC: ICH scores of 0-1 or an ICH score of 2 in combination with a negative in-situ-hybridization (ISH)
  - Or defined by ISH: negative ISH
Identifiable PD-L1 IC-status by central pathology (positive or negative) by means of VENTANA PD-L1 (SP142) assay; positive status is defined by PD-L1 expression on IC on ≥ 1% of the tumor area, negative status is defined by PD-L1 expression on IC on < 1% of the tumor area
No clinical evidence for distant metastasis (cM0)
Tumor block available for translational research
Performance Status Eastern Cooperative Oncology Group (ECOG) ≤ 1 or KI ≥ 80 %
Negative pregnancy test (urine or serum) within 7 days prior to screening in premenopausal patients
Women of childbearing potential and male patients with partners of childbearing potential must accept to implement a highly effective (less than 1% failure rate according to Pearl index) including at least one non-hormonal contraceptive measures during the study treatment and for 5 months following the last dose of study treatment such as:
- Intrauterine device (IUD)
- bilateral tubal occlusion
- vasectomized partner
- sexual abstinence
The patient must be accessible for treatment and follow-up
Normal cardiac function:
- Normal electrocardiogram (ECG) (within 6 weeks prior to screening)
- Normal left ventricular ejection fraction (LVEF) on echocardiorgraphy
Normal thyroid function

o Normal TSH and FT4
Blood counts within 14 days prior screening:
- absolute neutrophile count (ANC) must be ≥ 1,500/mm3
- Platelet count must be ≥ 100,000 / mm3
- Hemoglobin must be ≥ 10 g/dl
Hepatic functions:
- Total bilirubin must be ≤ 1 upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation > 1 x ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin
- Alkaline phosphatase must be ≤ 2.5 x ULN for the lab
- AST and ALT must be ≤1.5 x ULN for the lab.
- Patients with AST and ALT or alkaline phosphatase > 1 x ULN are eligible for inclusion if liver imaging (computerized tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET-CT, or PET scan) performed within 3 months prior to randomization (and part of standard of care) does not demonstrate metastatic disease and the requirements in criterion (just above) are met
- Patients with alkaline phosphatase that is > 1 x ULN but less than or equal to 2.5 x ULN or with unexplained bone pain are eligible if bone imaging does not demonstrate metastatic disease.
- Creatinine clearance ≥ 40 ml/min performed 28 days prior to screening

Exclusion Criteria:

Previous history of malign diseases, non-melanoma skin cancer and carcinoma of the cervix are allowed if treated with curative intent
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 Paclitaxel, Carboplatin, Epirubicin, Cyclophosphamide or Atezolizumab
Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol
Concurrent treatment with other drugs that are contraindicating the use of the study drugs
Existing pregnancy
Breastfeeding
Sequential breast cancer
Concurrent treatment with other experimental drugs and participation in another clinical trial or clinical research project (except registry study) within 30 days prior to study entry
Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including but not confined to:
- Uncompensated chronic heart failure or systolic dysfunction (LVEF < 55%, congestive heart failure (CHF) New York Heart Association (NYHA) classes II-IV),
- unstable arrhythmias requiring treatment i.e., atrial tachycardia with a heart rate ≥ 100/bpm at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher grade AV-block,
- Angina pectoris within the last 6 months requiring anti-anginal medication,
- Clinically significant valvular heart disease,
- Evidence of myocardial infarction on electrocardiogram (ECG),
- Poorly controlled hypertension (e.g., systolic > 180 mmHg or diastolic > 100 mmHg).
Inadequate organ function including but not confined to:
- hepatic impairment as defined by bilirubin > 1.5 x ULN
- pulmonary disease (severe dyspnea at rest requiring oxygen therapy)
Abnormal blood values:
- Platelet count below 100,000/mm3
- AST/ALT > 1.5 x ULN
- Hypokalaemia > CTCAE grade 1
- Neutropenia > CTCAE grade 1
- Anaemia > CTCAE grade 1
Administration of a live, attenuated vaccine within 4 weeks before cycle 1 day 1 or anticipation that such a vaccine will be required during the study
Treatment with systemic immunosuppressive medications (including but not limited to interferons, IL-2) within 28 days or 5 half-lives of the drug, whichever is longer, prior to randomization.
Treatment with systemic immunosuppressive medications (including but not limited to Prednisone, Cyclophosphamide, Azathioprine, Methotrexate, Thalidomide, and anti-tumor necrosis [anti-TNF] factor agents) within 14 days prior to screening or anticipation of need for systemic immunosuppressive medications during the study
Patients with prior allogeneic stem cell or solid organ transplantation
Active or history of autoimmune disease or immune deficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions:
- Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
- Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are permitted provided all of following conditions are met: Rash must cover < 10% of body surface area; Disease is well controlled at baseline and requires only low-potency topical corticosteroids; No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, Methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral Corticosteroids within the previous 12 months.
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
History of HIV infection, hepatitis B or hepatitis C infection.
Patients with significant cardiovascular disease
Patients with inadequate hematological and end-organ function
Patients receiving therapeutic anti-coagulants
Stage N3, as soon as 21 patients with stage N3 are randomized

Name	Affiliation	Role
Iris Reiser, Dr.	Palleos Healthcare GmbH	Study Director
Hans-Christian Kolberg, Prof. Dr.	Marienhospital Bottrop gGmbH; Klinik für Frauenheilkunde und Geburtshilfe; 46236 Bottrop	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Marienhospital Bottrop gGmbH; Klinik für Frauenheilkunde und Geburtshilfe;		Bottrop		46236	Germany

PubMed Identifier	Type	Citation	Retractions
26923782	Background	Alme AK, Karir BS, Faltas BM, Drake CG. Blocking immune checkpoints in prostate, kidney, and urothelial cancer: An overview. Urol Oncol. 2016 Apr;34(4):171-81. doi: 10.1016/j.urolonc.2016.01.006. Epub 2016 Feb 28.
17387718	Background	Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007 May 1;109(9):1721-8. doi: 10.1002/cncr.22618.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Oct 24, 2023

Arm/Group Information

ID	Title	Description
BG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
BG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00048.57± 11.66 BG00149.98± 12.34 BG00249.27± 12.01

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000179 BG001179 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Germany

Title	Measurements
	BG000180 BG001179 BG002

ECOG

ECOG scales (Eastern Cooperative Oncology Group Performance Status) are 0-to-5 rating systems used in oncology to assess a cancer patient's functional ability and overall well-being, helping doctors decide on treatments, predict outcomes, and determine eligibility for clinical trials, with 0 being fully active and 5 being deceased, reflecting a patient's capacity for daily activities, self-care, and work

Count of Participants

Participants

Title

Denominators

Categories

ECOG = 0

Title	Measurements
	BG000169 BG001

HER2 IHC status

HER2 IHC (Immunohistochemistry) status describes the amount of HER2 protein on cancer cells, scored 0 to 3+; 3+ means HER2-Positive (lots of protein, good for targeted drugs), 0 or 1+ usually means HER2-Negative, and 2+ is Equivocal/Borderline, requiring further testing (like FISH) for confirmation, with newer categories like HER2-Low (1+ or 2+/ISH-negative) now recognized for specific therapies.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00072 BG001

Tumor histology

Breast tumor histology examines cell structure, differentiation, and arrangement (like tubules, nests, or single files) to classify tumors (e.g., ductal, lobular, mucinous, papillary) and grade aggressiveness (e.g., tubule formation, nuclear pleomorphism, mitotic count), revealing key features like invasion of basement membranes (invasive carcinoma) versus confined growth (DCIS), crucial for diagnosis, prognosis, and treatment planning.

Count of Participants

Participants

Title

Denominators

Categories

INFILTRATING DUCTAL

Title	Measurements
	BG000171 BG001

Tumor grading

Tumor grading is a system that classifies cancer cells based on how abnormal they look under a microscope, indicating their likely behavior (how fast they grow and spread). Grades typically range from 1 to 4, with Grade 1 (well-differentiated) cells resembling normal cells and growing slowly, while Grade 4 (undifferentiated/poorly differentiated) cells look very abnormal, grow aggressively, and spread quickly. This grading helps doctors plan treatment and predict prognosis, working alongside cancer staging (which describes the tumor's size and spread).

Count of Participants

Participants

Title

Denominators

Categories

GRADE 2

Title	Measurements
	BG00021 BG001

Tumor stage

In breast cancer staging, the "cT" refers to the clinical tumor stage, determined by physical exam/imaging (like CT scans), describing the primary tumor's size and local spread (e.g., T1, T2, T3, T4), indicating if it's small, large, or growing into skin/chest wall, a crucial part of the TNM system (Tumor, Nodes, Metastasis) that helps define the cancer's extent before treatment begins.

Count of Participants

Participants

Title

Denominators

Categories

cT1c

Title	Measurements
	BG00073 BG001

Nodal status

Nodal status in breast cancer refers to whether cancer cells have spread to nearby lymph nodes (usually under the arm), a key factor for staging, prognosis, and treatment planning, classified under the TNM system (N0 for no spread, N1-N3 for increasing involvement). It's assessed via sentinel lymph node biopsy or axillary dissection, with positive nodes indicating higher risk, guiding decisions for systemic therapies like chemotherapy, even if the primary tumor seems small.

Count of Participants

Participants

Title

Denominators

Categories

cN0

Title	Measurements
	BG000123 BG001

HER2 status

Count of Participants

Participants

Title

Denominators

Categories

LOW (IHC 1+ or 2+/ISH negative)

Title	Measurements
	BG000108 BG001

Hormone receptor status

Count of Participants

Participants

Title

Denominators

Categories

Borderline Positive (either ER or PR expression is above 1% and <10%)

Title	Measurements
	BG00025 BG00133 BG002

Weight (kg)

Median

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00072.00± 13.52 BG00170.36± 13.65 BG002

Percentage of Positive KI-67 Cells

Positive Ki-67 cells are cells actively dividing or preparing to divide, identified by the presence of the Ki-67 protein, a key marker for cell proliferation used in cancer diagnosis to gauge tumor aggressiveness (proliferation index) and predict treatment response, especially in breast cancer, where higher percentages often signal faster-growing tumors, though cutoffs vary.

Mean

Standard Deviation

percentage

Title

Denominators

Categories

Title	Measurements
	BG00069.28± 17.97 BG001

Cellularity (percentage of tumor volume occupied by invasive tumors cells)

Cellularity in breast cancer refers to the density or proportion of cancer cells within the tumor, a key factor pathologists assess in tissue samples (H&E slides) to gauge tumor aggressiveness, treatment response (especially after neoadjuvant therapy), and patient prognosis, often linked to tumor size and vascular invasion, with high cellularity sometimes indicating worse outcomes.

Mean

Standard Deviation

percentage

Title

Denominators

Categories

Title	Measurements
	BG00039.22± 20.17 BG001

TILs (percentage)

Tumor-infiltrating lymphocytes (TILs) are immune cells found within and around breast cancer tumors. Their presence indicates the body is mounting an anti-tumor immune response and serves as an important prognostic and predictive biomarker, especially in certain breast cancer subtypes, whereby a higher percentage is often associated with a better prognosis.

Mean

Standard Deviation

percentage

Title

Denominators

Categories

Title	Measurements
	BG00024.68± 19.64 BG001

PD-L1 expression

PD-L1 expression is primarily measured in tumor tissue samples using immunohistochemistry (IHC), a laboratory technique where pathologists visually assess stained tissue under a microscope. This measurement helps determine if a patient is likely to benefit from immune checkpoint inhibitor therapies (immunotherapy).

Mean

Standard Deviation

percentage

Title

Denominators

Categories

Title	Measurements
	BG0001.12± 2.77 BG001

Largest tumor diameter

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00024.79± 2.47 BG00125.34± 11.52 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Pathological Complete Response (ypT0/is, ypN0)

Pathological Complete Response defined as no residual invasive tumor cells in the breast and in the lymph nodes (ypT0/is, ypN0).

The analysis was performed in the ITT population. The analysis population for the primary endpoint encompassed 339 patients with available pCR status (10 missing in each arm).

Posted

Count of Participants

Participants

after 29-30 weeks in Arm A and after 27-28 weeks in Arm B.

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Units	Counts
Participants	OG000170 OG001169

Title

Denominators

Categories

pCR = 0 (no pCR)

Title	Measurements
	OG00058 OG00152

pCR = 1 (pCR achieved)

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This was a randomized, open-label, adaptive, two arm, multicenter phase II trial that enrolled female and male patients with primary TNBC (defined as ER/PR < 10% and HER2-negative) with tumor stages cT1c - cT4d (cN0 and cN+). Patients were randomized to Arm A and B, stratified by PD-L1 expression on immune cells (IC-status) and anatomic tumor stage (Anatomic Stage Groups I, II and III). PD-L1 status was determined by central pathology using the VENTANA PD-L1 (SP142) assay.					Risk Difference (RD)	-0.0327			2-Sided	95	-0.1307	0.0663					Superiority	The primary analysis uses Bayesian statistics for proportions, and is based on non-informative uniform (beta) priors for the pCR rates pA and pB in arms A (experimental) and B (control) respectively. Similar to a proof-of-concept trial, a dual criterion to simultaneously test for significant and relevant superiority at different levels of certainty was used, by requiring posterior probabilities, conditional on observed response counts xA, xB respectively in the two arms.

Secondary

Number of Adverse Events by Grade

Safety (incidence, relationship, seriousness, and severity of all AEs, SAEs, AESIs coded by medical dictionary for regulatory activities (MedDRA), summarized by Preferred Term and System Organ Class and graded according to common terminology criteria of adverse events (CTCAE V5.0)

Safety endpoints are based on a subset of the ITT population that actually received treatment. The safety population included 356 patients, 178 from Arm A and 178 from Arm B. Most frequent AEs (>10% of patients) by system organ class are shown.

Posted

Number

Adverse Events

from date of randomization up to 24 months

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Secondary

Pathological Complete Response (ypT0/is, ypN0) (ER/PR Expression of <1%).

Pathological complete response defined as no residual invasive tumor cells in the breast and in the lymph nodes (ypT0/is, ypN0) in patients with an ER/PR expression of <1% and an ER/PR expression of 1% to 10%.

Patients with an ER/PR expression of <1%. (Data for partients and an ER/PR expression of 1% to 10%, see below.)

Posted

Count of Participants

Participants

after 29-30 weeks in Arm A and after 27-28 weeks in Arm B

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B

Secondary

Pathological Complete Response (ypT0/is, ypN0) (ER/PR Between 1 and 10 %).

Patients with an ER/PR expression of 1% to 10%. (Data for partients an ER/PR expression of <1%, see above.)

Posted

Count of Participants

Participants

after 29-30 weeks in Arm A and after 27-28 weeks in Arm B

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B

Secondary

Pathological Complete Response (ypT0, ypN0)

Pathological complete response defined as no tumor cells (invasive and no non-invasive) in the breast but also in the lymph nodes (ypN0, ypT0).

Same as f0r Primary Endpoint.

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Count of Participants

Participants

after 29-30 weeks in Arm A and after 27-28 weeks in Arm B.

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Secondary

Near Pathological Complete Response (Near pCR)

Near pCR defined as residual tumor <5 mm in the breast irrespective of in situ and lymph nodes status

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Count of Participants

Participants

after 29-30 weeks in Arm A and after 27-28 weeks in Arm B.

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Secondary

Pathological Complete Response (no Invasive Tumor)

Pathological Complete Response defined as no invasive tumor in the breast, irrespective of lymph node status

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Count of Participants

Participants

after 29-30 weeks in Arm A and after 27-28 weeks in Arm B.

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Secondary

Decrease of Ki-67 Expression by ≥ 30% Compared to Baseline as Continuous Predictor After 14 (Arm A)/28 Days (armB) (+/- 2 Days) of Treatment

Decrease of Ki-67 expression versus baseline after 14/28 days (+/- 2 days) of treatment as continuous predictor.

General comment to analysis of secondary biomarker endpoints: biomarker endpoints are analysed as secondary efficacy endpoints. Biomarker endpoints are measured by core biopsy at a central pathology laboratory at two different timepoints. For arm A visit 1 (A1 in tables) corresponds to day 14 in the trial and denotes the measurement after the Atezolizumab monotherapy window. Arm A visit 3 (A3 in tables) corresponds to day 28 and denotes a measurement taken again after two weeks of combined immuno- and chemotherapy. In arm B, only visit 2 (day 14; B2 in tables) is measured after the initial two weeks of combined immuno- and chemotherapy.

Analyzed were available samples of participants (20 missing in arm A; 41 missing in arm B).

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Count of Participants

Participants

after 14/28 days (+/- 2 days) of treatment

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Secondary

Decrease of Ki-67 Expression After 28 Days (+/- 2 Days) of Treatment for Arm A and Arm B.

Decrease of Ki-67 expression versus baseline by 30% or more after 28 days (+/- 2 days) of treatment. See general comments to biomarker endpoints above. Decrease of Ki-67 defined as ≥ 30% compared to baseline.

Analyzed were all available samples of participants (43 missing in arm A; 41 missing in arm B).

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Count of Participants

Participants

after 28 days (+/- 2 days) of treatment

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B

Secondary

Stromal Tumor-infiltrating Lymphocytes (TILs) ≥ 60% After 14 (Arm A)/28 Days (ArmB)

TILs after 14/28 days (+/- 2 days) of treatment as continuous predictor. See general comments to biomarker endpoints above.

Analyzed were all available samples of participants (20 missing in arm A; 39 missing in arm B).

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Count of Participants

Participants

after 14/28 days (+/- 2 days) of treatment

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Secondary

Tumor-infiltrating Lymphocytes (TILs) ≥ 60% After 28 Days

TILs ≥ 60% after 28 days (+/- 2 days) of treatment. Stromal Tumor Infiltrating Lymphocytes (TILs) ≥ 60%.

See general comments to biomarker endpoints above.

Analyzed were all available samples of participants (42 missing in arm A; 39 missing in arm B).

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Count of Participants

Participants

after 28 days (+/- 2 days) of treatment

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Secondary

Complete Cell Cycle Arrest (CCCA) After 14 (Arm A)/28 Days (armB) (+/- 2 Days) of Treatment

Complete Cell Cycle Arrest (CCCA): Ki-67 expression ≤ 2.7% after 14/28 days (+/- 2 days) of treatment.

See general comments to biomarker endpoints above.

Analyzed were all available samples of participants (20 missing in arm A; 41 missing in arm B).

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Count of Participants

Participants

after 14/28 days (+/- 2 days) of treatment

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B

Secondary

Complete Cell Cycle Arrest (CCCA) After 28 Days (+/- 2 Days) of Treatment

CCCA: Ki-67 expression ≤ 2.7%. Complete Cell Cycle Arrest (CCCA) defined as : Ki-67 ≤ 2.7%.

See general comments to biomarker endpoints above.

Analyzed were all available samples of participants (43 missing in arm A; 41 missing in arm B).

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Count of Participants

Participants

after 28 days (+/- 2 days) of treatment

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Secondary

Low Cellularity (< 500 Tumor Cells) After 14 (Arm A)/28 Days (Arm B) (+/- 2 Days) of Treatment

Low cellularity: < 500 tumor cells after 14/28 days (+/- 2 days) of treatment. See general comments to biomarker endpoints above.

Analyzed were all available samples of participants (20 missing in arm A; 37 missing in arm B).

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Count of Participants

Participants

after 14/28 days (+/- 2 days) of treatment

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Secondary

Low Cellularity (< 500 Tumor Cells) After 28 Days (+/- 2 Days) of Treatment

Low cellularity: < 500 tumor cells after 28 days (+/- 2 days) of treatment. See general comments to biomarker endpoints above.

Analyzed were all available samples of participants (41 missing in arm A; 37 missing in arm B).

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Count of Participants

Participants

after 28 days (+/- 2 days) of treatment

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Secondary

Combined Early Response After 14 (Arm A)/28 (Arm B) Days (+/- 2 Days) of Treatment

Combined early response defined by

CCCA (Ki-67 expression < 2.7%) or
low cellularity or
decrease of Ki-67 expression (versus baseline) by 30% or more or
TILs ≥ 60% See general comments to biomarker endpoints above.

Analyzed were all available samples of participants (19 missing in arm A; 37 missing in arm B).

Posted

Count of Participants

Participants

after 14/28 days (+/- 2 days) of treatment

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B

Secondary

Combined Early Response After 28 Days (+/- 2 Days) of Treatment

Combined early response defined by

CCCA (Ki-67 expression < 2.7%) or
low cellularity or
decrease of Ki-67 expression (versus baseline) by 30% or more or
TILs ≥ 60% See general comments to biomarker endpoints above.

Analyzed were all available samples of participants (41 missing in arm A; 37 missing in arm B).

Posted

Count of Participants

Participants

after 28 days (+/- 2 days) of treatment

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B

Secondary

Disease Free Survival (DFS)

Disease free survival (DFS) defined as time from the first date of no disease [i.e. date of surgery] to the first occurrence of disease recurrence or death from any cause.

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Count of Participants

Participants

from randomization up to 24 months until date of occurrence of no disease to the first occurrence of disease recurrence or death from any cause

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Secondary

Overall Survival (OS).

Overall survival (OS) defined as length of time from randomization to death from any cause. Given that novel post-neoadjuvant treatment options (on and off-trial) have emerged such as Pembrolizumab, the post-neoadjuvant treatment in the follow-up phase of this study would have been most certainly highly heterogeneous. Thus, completion of follow-up to 3 years was no longer justified. Therefore, follow-up was limited to 2 years and only clinically significant survival signals were observed.

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Count of Participants

Participants

from randomization up to 24 months until date of death from any cause.

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001

Secondary

Event Free Survival (EFS)

Event free survival (EFS) defined as length of time after randomization till death from any cause, failure to achieve remission after induction therapy, relapse in any site, or second malignancy

Posted

Count of Participants

Participants

from randomization up to 24 months until date of death from any cause, failure to achieve remission after induction therapy, relapse in any site, or second malignancy

ID	Title	Description
OG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.
OG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A	2 weeks Atezolizumab monotherapy before biopsy, followed by a 12-week therapy with Paclitaxel + Carboplatin+ Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 840 MG in 14 ML Injection: 840 mg Day 1 for two weeks Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm A: 1st Biopsy two weeks after Baseline visit. 2nd Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 3rd Biopsy with tumor size greater 10 mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.	1	180	86	178	178	178
EG001	Arm B	12-week therapy with Paclitaxel + Carboplatin + Atezolizumab every 3 weeks for 4 cycles. This will be followed by Epirubicin + Cyclophosphamide + Atezolizumab every 3 weeks for 4 cycles. Atezolizumab 1200 MG in 20 ML Injection: 1200 mg Day 1 every 3 weeks for 8 cycles Carboplatin: Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles Paclitaxel: Paclitaxel 80 mg/m² IV weekly x 12 cycles Epirubicin: 90 mg/m2, day 1 for 4 cycles (12 weeks) Cyclophosphamide: 600 mg/m2, day 1 for 4 cycles (12 weeks) Biopsy Arm B: 1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter. Surgery: After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.	0	179	87	178	178	178

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0007 affected178 at risk EG0017 affected178 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG00023 affected178 at risk EG00121 affected178 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected178 at risk EG00110 affected178 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0009 affected178 at risk EG0015 affected178 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Immune-mediated myocarditis	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Addison's disease	Endocrine disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Visual acuity reduced	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Anal fissure	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected178 at risk EG0011 affected178 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Device related thrombosis	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Fatigue	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
General physical health deterioration	General disorders	MedDRA 10.0	Systematic Assessment	EG00012 affected178 at risk EG0019 affected178 at risk
Non-cardiac chest pain	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Pyrexia	General disorders	MedDRA 10.0	Systematic Assessment	EG00022 affected178 at risk EG00112 affected178 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0012 affected178 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected178 at risk EG0010 affected178 at risk
Hypersensitivity	Immune system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0012 affected178 at risk
Immune-mediated adverse reaction	Immune system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Atypical pneumonia	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0011 affected178 at risk
Catheter site infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0002 affected178 at risk EG0011 affected178 at risk
Coronavirus infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
COVID-19	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0002 affected178 at risk EG0010 affected178 at risk
Device related infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Diverticulitis intestinal perforated	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Febrile infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0013 affected178 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0003 affected178 at risk EG0012 affected178 at risk
Influenza	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Ophthalmic herpes zoster	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Peritonsillar abscess	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Pneumonia	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0012 affected178 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Post-acute COVID-19 syndrome	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Sepsis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0011 affected178 at risk
Septic shock	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Urinary tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0003 affected178 at risk EG0012 affected178 at risk
Wound infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Alanine aminotransferase	Investigations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Blood creatinine increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0011 affected178 at risk
C-reactive protein increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Ejection fraction decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Liver function test increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Medical observation	Investigations	MedDRA 10.0	Systematic Assessment	EG0002 affected178 at risk EG0010 affected178 at risk
Neutrophil count decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0003 affected178 at risk EG0015 affected178 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0012 affected178 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0012 affected178 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Dizziness	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Facial paralysis	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Fine motor skill dysfunction	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Headache	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Meningism	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0011 affected178 at risk
Nephritis	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Renal failure	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Bronchospasm	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected178 at risk EG0010 affected178 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0012 affected178 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Skin reaction	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Central venous catheter removal	Surgical and medical procedures	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk
Hospitalisation	Surgical and medical procedures	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0010 affected178 at risk
Thrombosis	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected178 at risk EG0011 affected178 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG00093 affected178 at risk EG001108 affected178 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG00051 affected178 at risk EG00149 affected178 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG000106 affected178 at risk EG00198 affected178 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG00066 affected178 at risk EG00166 affected178 at risk
Constipation	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00044 affected178 at risk EG00152 affected178 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00046 affected178 at risk EG00158 affected178 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00022 affected178 at risk EG00125 affected178 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00091 affected178 at risk EG00199 affected178 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00024 affected178 at risk EG00131 affected178 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00040 affected178 at risk EG00126 affected178 at risk
Fatigue	General disorders	MedDRA 10.0	Systematic Assessment	EG00098 affected178 at risk EG001105 affected178 at risk
Mucosal inflammation	General disorders	MedDRA 10.0	Systematic Assessment	EG00039 affected178 at risk EG00121 affected178 at risk
Pyrexia	General disorders	MedDRA 10.0	Systematic Assessment	EG00044 affected178 at risk EG00126 affected178 at risk
Alanine aminotransferase increased	Investigations	MedDRA 10.0	Systematic Assessment	EG00047 affected178 at risk EG00137 affected178 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 10.0	Systematic Assessment	EG00035 affected178 at risk EG00121 affected178 at risk
Neutrophil count decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG00038 affected178 at risk EG00147 affected178 at risk
Platelet count decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG00019 affected178 at risk EG00133 affected178 at risk
White blood cell count decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG00018 affected178 at risk EG00129 affected178 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG00018 affected178 at risk EG00123 affected178 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG00031 affected178 at risk EG00132 affected178 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG00028 affected178 at risk EG00132 affected178 at risk
Dysgeusia	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00016 affected178 at risk EG00120 affected178 at risk
Headache	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00039 affected178 at risk EG00141 affected178 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00029 affected178 at risk EG00125 affected178 at risk
Polyneuropathy	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00043 affected178 at risk EG00150 affected178 at risk
Insomnia	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG00020 affected178 at risk EG00121 affected178 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG00023 affected178 at risk EG00127 affected178 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG00037 affected178 at risk EG00131 affected178 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00091 affected178 at risk EG00199 affected178 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00019 affected178 at risk EG00122 affected178 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00032 affected178 at risk EG00127 affected178 at risk
Hot flush	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG00032 affected178 at risk EG00121 affected178 at risk
Tachycardia	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0005 affected178 at risk EG0019 affected178 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 10.0	Systematic Assessment	EG00013 affected178 at risk EG00117 affected178 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 10.0	Systematic Assessment	EG00012 affected178 at risk EG00110 affected178 at risk
Hypothyroidism	Endocrine disorders	MedDRA 10.0	Systematic Assessment	EG0008 affected178 at risk EG00112 affected178 at risk
Dry eye	Eye disorders	MedDRA 10.0	Systematic Assessment	EG00011 affected178 at risk EG0018 affected178 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0007 affected178 at risk EG00111 affected178 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00017 affected178 at risk EG00111 affected178 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG00010 affected178 at risk EG0019 affected178 at risk
Oral pain	General disorders	MedDRA 10.0	Systematic Assessment	EG0009 affected178 at risk EG0015 affected178 at risk
Chills	General disorders	MedDRA 10.0	Systematic Assessment	EG00014 affected178 at risk EG00110 affected178 at risk
Influenza like illness	General disorders	MedDRA 10.0	Systematic Assessment	EG00010 affected178 at risk EG0015 affected178 at risk
Mucosal dryness	General disorders	MedDRA 10.0	Systematic Assessment	EG0009 affected178 at risk EG00111 affected178 at risk
Oedema	General disorders	MedDRA 10.0	Systematic Assessment	EG0005 affected178 at risk EG00113 affected178 at risk
Oedema peripheral	General disorders	MedDRA 10.0	Systematic Assessment	EG00010 affected178 at risk EG00111 affected178 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG00016 affected178 at risk EG00111 affected178 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 10.0	Systematic Assessment	EG00011 affected178 at risk EG0018 affected178 at risk
Hypersensitivity	Immune system disorders	MedDRA 10.0	Systematic Assessment	EG0009 affected178 at risk EG0017 affected178 at risk
Cystitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG00011 affected178 at risk EG0014 affected178 at risk
Urinary tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG00011 affected178 at risk EG0016 affected178 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG00014 affected178 at risk EG00113 affected178 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0008 affected178 at risk EG00111 affected178 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 10.0	Systematic Assessment	EG00012 affected178 at risk EG00110 affected178 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0008 affected178 at risk EG00115 affected178 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG00014 affected178 at risk EG0019 affected178 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG00011 affected178 at risk EG0018 affected178 at risk
Dizziness	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00011 affected178 at risk EG00110 affected178 at risk
Paraesthesia	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0008 affected178 at risk EG00111 affected178 at risk
Taste disorder	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG00014 affected178 at risk EG00111 affected178 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG00013 affected178 at risk EG00115 affected178 at risk
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG00010 affected178 at risk EG00112 affected178 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0009 affected178 at risk EG0017 affected178 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG00011 affected178 at risk EG0016 affected178 at risk
Skin reaction	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected178 at risk EG0019 affected178 at risk
Skin toxicity	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0008 affected178 at risk EG0019 affected178 at risk

ID	Term
D001943	Breast Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
C000594389	atezolizumab
D007267	Injections
D016190	Carboplatin
D017239	Paclitaxel
D000068196	Albumin-Bound Paclitaxel
D015251	Epirubicin
D003520	Cyclophosphamide
D013514	Surgical Procedures, Operative

ID	Term
D004333	Drug Administration Routes
D004358	Drug Therapy
D013812	Therapeutics
D056831	Coordination Complexes
D009930	Organic Chemicals
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D004224	Diterpenes
D013729	Terpenes
D000418	Albumins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D004317	Doxorubicin
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D011083	Polycyclic Compounds
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D063088	Phosphoramides
D009943	Organophosphorus Compounds