Study to Compare a Mono Atezolizumab Window Followed by a Atezolizumab - CTX Therapy With Atezolizumab - CTX Therapy

NCT04770272 | Terminated Phase 2 Results DMC

• 1 other identifier: Phaon1
• Study Type: interventional
• Target: 442
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, adaptive, two arm, multicentre, Phase II trial comparing a neoadjuvant chemotherapy with PDL1-inhibition (Atezolizumab) and Atezolizumab two-week window to chemotherapy with PDL1-inhibition (Atezolizumab) and identify biomarkers predicting (early) response to or resistance against Atezolizumab (alone and with CTX) allowing patients stratification in future clinical trials

Conditions

Triple-negative Breast Cancer

Keywords

TNBC; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (19)

• Number of Adverse Events by Grade

  from date of randomization up to 24 months

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

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

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

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

• Pathological Complete Response (ypT0, ypN0)

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

• Near Pathological Complete Response (Near pCR)

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

Study Arms (2)

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

Interventions

Atezolizumab 840 MG in 14 ML Injection DRUG

840 mg Day 1 for two weeks

Also known as: Tecentriq

Arm A

Atezolizumab 1200 MG in 20 ML Injection DRUG

1200 mg Day 1 every 3 weeks for 8 cycles

Also known as: Tecentriq

Arm A; Arm B

Carboplatin DRUG

Dosing according to Area Under the Curve of 2 Intravenous weekly x 12 cycles

Also known as: Paraplatin

Arm A; Arm B

Paclitaxel DRUG

Paclitaxel 80 mg/m² IV weekly x 12 cycles

Also known as: Abraxane, Onxol

Arm A; Arm B

Epirubicin DRUG

90 mg/m2, day 1 for 4 cycles (12 weeks)

Also known as: Paxene

Arm A; Arm B

Cyclophosphamide DRUG

600 mg/m2, day 1 for 4 cycles (12 weeks)

Also known as: Cytoxan

Arm A; Arm B

Biopsy Arm A PROCEDURE

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.

Arm A

Biopsy Arm B PROCEDURE

1st Biopsy after two weeks of Carboplatin + Paclitaxel + Atezolizumab therapy. 2nd Biopsy with tumor size greater 10mm in diameter.

Arm B

Surgery PROCEDURE

After completion of 27-28 weeks (Arm B) or 29-30 weeks (Arm A) of neoadjuvant treatment, surgery is planned for all patients.

Arm A; Arm B

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Palleos Healthcare GmbH: lead
• Roche Pharma AG: collaborator
• Phaon Scientific GmbH: collaborator
• University Hospital, Essen: collaborator
• University Hospital Erlangen: collaborator

Study Sites (1)

Marienhospital Bottrop gGmbH; Klinik für Frauenheilkunde und Geburtshilfe;

Bottrop, 46236, Germany

Location

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• Yi M, Huo L, Koenig KB, Mittendorf EA, Meric-Bernstam F, Kuerer HM, Bedrosian I, Buzdar AU, Symmans WF, Crow JR, Bender M, Shah RR, Hortobagyi GN, Hunt KK. Which threshold for ER positivity? a retrospective study based on 9639 patients. Ann Oncol. 2014 May;25(5):1004-11. doi: 10.1093/annonc/mdu053. Epub 2014 Feb 20.

  PMID: 24562447 BACKGROUND

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

atezolizumab; Injections; Carboplatin; Paclitaxel; Albumin-Bound Paclitaxel; Epirubicin; Cyclophosphamide; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

Although the trial had to stop recruitment prematurely after a first planned interim analysis of the first 100 pCR results (given that a probability of less than 2.5% of meeting the primary endpoint was estimated), 442 patients had already been screened and 363 had been randomized and were allowed to continue therapy.

Results Point of Contact

• Title: Palleos | CRO Germany
• Organization: Palleos healthcare GmbH

info@palleos.com

+496119501900

Study Officials

• 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

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: February 25, 2021
• Study Start: March 1, 2021
• Primary Completion: July 6, 2023
• Study Completion: October 2, 2024
• Last Updated: January 12, 2026
• Results First Posted: January 12, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)