A Study Evaluating the Efficacy and Safety of Adjuvant Atezolizumab or Placebo and Trastuzumab Emtansine for Participants With HER2-Positive Breast Cancer at High Risk of Recurrence Following Preoperative Therapy (Astefania)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Apr 2021 → ongoing

Decision date (initial)

2024-03-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

F. Hoffmann La Roche

External identifiers

EU CT number

2023-503568-18-00

EudraCT number

2020-003681-40

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Efficacy, Safety

To evaluate the efficacy of atezolizumab when given in combination with trastuzumab emtansine compared with placebo and trastuzumab emtansine in the Full Analysis Set (FAS).

Secondary objectives 4

1. To evaluate the efficacy of atezolizumab when given in combination with trastuzumab emtansine compared with placebo and trastuzumab emtansine on the basis of IDFS including second primary non breast invasive cancer, disease free survival, overall survival, distant recurrence-free interval, the proportion of patients in each arm with clinically meaningful deterioration in global health status/quality of life (GHS/QoL) assessed via the European Organisation for Research and Treatment of Cancer quality of life questionnaire for cancer, mean absolute scores and mean change from baseline scores in GHS/QoL, physical, role, cognitive function
2. To evaluate safety of atezolizumab when given in combination with trastuzumab emtansine compared with placebo and trastuzumab emtansine
3. To characterize pharmacokinetic profiles of atezolizumab and trastuzumab emtansine
4. To evaluate immune response to atezolizumab and trastuzumab emtansine

Conditions and MedDRA coding

Early human epidermal growth factor receptor 2 (HER2) positive breast cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically confirmed invasive breast carcinoma
2. Pathologic evidence of residual invasive carcinoma in the breast and/or axillary lymph node(s) at surgery after completion of neoadjuvant therapy. Positive nodal residual disease, with or without residual invasive disease in the breast, is mandatory in patients with cT1-3/N0-1/M0 disease at presentation.
3. Diagnosis of HER2-positive breast cancer with assessment of hormone receptor and programmed death ligand 1 status , as documented through central testing of a representative tumor tissue specimen
4. Completion of preoperative systemic chemotherapy and HER2-directed treatment
5. Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes
6. An interval of no more than 12 weeks between the date of primary surgery and the date of randomization

Exclusion criteria 6

1. Stage IV (metastatic) breast cancer
2. Inadequate excision
3. An overall response of disease progression according to the investigator at the conclusion of preoperative systemic therapy
4. Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons
5. History of other malignancy within 5 years prior to screening
6. Prior treatment with atezolizumab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Invasive disease-free survival

Secondary endpoints 10

1. 1. Invasive disease-free survival including second primary non breast invasive cancer
2. 2. IDFS, in the PD-L1-positive and the PD-L1-negative population (defined as all randomized patients from the ITT population with a centrally assessed PD-L1-positive [i.e., PD-L1 status of IC1/2/3] or PD-L1-negative status [i.e.,PD-L1 status of IC0] at randomization as per corresponding stratification factors recorded in the IWRS).
3. 3. Disease-free survival
4. 4 . Overall survival
5. 5 . Distant recurrence-free interval
6. 6. The proportion of patients in each arm with clinically meaningful deterioration in GHS/QoL physical, role, and cognitive function as measured by scales of the European Organisation for Research and Treatment of Cancer quality of life questionnaire for cancer (EORTC QLQ C30)
7. 7. Mean absolute scores and mean change from baseline scores in GHS/QoL, physical, role, and cognitive function, as assessed using the EORTC QLQ C30
8. 8. Incidence and severity of adverse events
9. 9. Maximum and minimum serum concentrations for atezolizumab and trastuzumab emtansine
10. 10. Incidence of antidrug antibodies (ADAs) to atezolizumab and to trastuzumab emtansine at specified timepoints

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 6

Locations

14 EU/EEA countries · 109 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 169 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications