Early stage HER2-positive breast cancer (T stage >= T3, lymph node positive, or inflammatory) MedDRA version: 21.0 Level: LLT Classification code 10025541 Term: Malignant breast neoplasm System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Bentadax
Product Name: Paclitaxel
Product Code: [na]
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: PACLITAXEL
CAS Number: 33069-62-4
Current Spo
Sponsors
ASTRAZENECA AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients must be at least 18 years of age. - Histologically documented HER2-positive EBC participants with: (a) locally assessed HER2-positive (IHC 3+ or ISH+) according to ASCOCAP guidelines and prospectively centrally confirmed as HER2 positive based on a tumour sample (b) unifocal and multifocal tumours (> 1 tumour confined to the same quadrant as the primary tumour) must have 1 focus sampled and centrally confirmed as HER2 positive (c) multi-centric tumours (multiple tumours involving > 1 quadrant of the breast) must have 1 lesion from each involved quadrant sampled and centrally confirmed as HER2 positive. All quadrants tested must be centrally confirmed as HER2 positive (d) tumours documented as HR-positive (either ER and/or PgR positive [ER or PgR >= 1%]) or HR-negative (ER and PgR negative) by local assessment per ASCO-CAP guidelines (Allison et al 2020) (e) clinical stage at presentation (based on mammogram or breast MRI assessment): T0-4 (inclusive of inflammatory breast cancer), N1-3, M0 or = T3, N0, M0 as determined by the AJCC staging system, 8th edition (Hortobagyi et al 2017) (f) pathologic confirmation of nodal involvement with malignancy as determined by fine-needle aspiration or core-needle biopsy, when applicable. - FFPE tissue block (2 cores) or 20 freshly-cut, serial tumor slides for HER2 assessment by central lab. If blocks are incomplete or fewer than 20 slides are available, participants may be eligible following discussion with the AstraZeneca Study Physician - ECOG performance status of 0 or 1 at randomization - Adequate organ and bone marrow function - LVEF >= 50% within 28 days before randomization Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 530 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 94
Exclusion criteria
Exclusion criteria: - Prior history of invasive breast cancer - Any primary malignancy within 3 years, except adequately resected non-melanoma skin cancer, or curatively treated in situ disease - History of DCIS, except for participants treated with mastectomy only > 5 years prior to current diagnosis - Prior sentinel lymph node biopsy or axillary lymph node dissection before initiation of neoadjuvant treatment - Prior systemic therapy for the treatment of breast cancer - Previous treatment with anthracyclines, cyclophosphamide or taxanes for any malignancy; cyclophosphamide allowed for non-cancer treatment if last dose > 6 months - Ineligible for any medication in the control Arm C - Any concurrent anticancer treatment - History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening - Lung-specific intercurrent clinically significant illnesses including, but not limited to, any pulmonary disorder - Investigator judgement of 1 or more of the following: (a) mean resting corrected QTcF interval of >470 ms (females) or >450 ms (males) (b) history of QT prolongation associated with other medications that required discontinuation of that medication or any medication known to prolong QT interval and cause TdP. (c) congenital long QT syndrome, family history of long QT syndrome or unexplained death under 40 years in first degree relatives - History of arrhythmia, symptomatic or uncontrolled atrial fibrillation or asymptomatic sustained ventricular tachycardia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This is a Phase 3, open-label, three-arm study to determine the safety and efficacy of T-DXd monotherapy or T-DXd followed by THP as neoadjuvant treatment compared to standard of care (ddAC-THP) in participants with locally advanced or inflammatory HER2-positive early breast cancer. The target population of interest in this study is participants with highrisk HER2-positive early breast cancer. Participants will be randomized in a 1:1:1 ratio to one of the following intervention groups: T DXd monotherapy (Arm A), T-DXd followed by THP (Arm B), or ddAC-THP (Arm C). The primary objective is to demonstrate the superiority of neoadjuvant T-DXd alone or in sequence with THP relative to ddAC-THP by assessment of pCR (pathological complete response, ypT0/Tis ypN0) using central evaluation in participants with HER2-positive early breast cancer.;Secondary Objective: To assess the effectiveness of neoadjuvant T-DXd alone or in sequence with THP relative to ddAC-THP by assessment of a (i) secondary definition of pCR (ypT0/Tis ypN0) using central evaluation, (ii) 3-year EFS (event-free survival), (iii) 3-year IDFS (invasive-disease free survival), and (iv) OS (overall survival). Data will also be collected to demonstrate the tolerability, safety, immunogenicity and PK of the investigational product.;Primary end point(s): pCR (ypT0/Tis ypN0): Rate of pCR is defined as the proportion of participants who have no evidence by H&E staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by central evaluation following completion of neoadjuvant therapy.;Timepoint(s) of evaluation of this end point: Patients should undergo surgery no later than 6 weeks following administration of the last cycle of the randomized treatment. Surgical specimens will be sent for central assessment of pCR. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) pCR (ypT0/Tis ypN0): Rate of pCR is defined as the proportion of participants who have no evidence by H&E staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by central evaluation following completion of neoadjuvant therapy. 2) EFS 3) IDFS 4) OS 5) HRQoL: Symptomatic AEs assessed by the PRO CTCAE and items from the EORTC Item Library. Overall side-effect bother measured by PGI-TT at each time point in each treatment arm. Physical function assessed by the EORTC QLQ-C30 Physical Function Scale. The measure of interest will be the proportion of participants who have maintained or improved physical functioning while on neoadjuvant treatment, as measured by EORTC QLQ-C30 at each time point in each treatment arm. 6) Safety and Tolerability: Safety and tolerability will be evaluated in terms of occurrence of AEs, SAEs and changes from baseline in vital signs, clinical laboratory results, ECGs, and ECHO/MUGA. Heart failure: NYHA Class III and IV heart failure during the neoadjuvant treatment period (pre- and post-surgery) and at end of study. Decreases in LVEF will be evaluated by determining the percentage of participants with decreases in LVEF of at least 10 points from baseline and to below 50% during neoadjuvant treatment period (pre- and postsurgery). 7) PK of T-DXd: Serum concentration of T-DXd, anti-HER2 antibody, and DXd. 8) Immunogenicity for T-DXd: Number and percentage of participants who develop ADAs for T-DXd. | — |
Countries
Austria, Brazil, Bulgaria, Canada, China, Germany, India, Italy, Japan, Korea, Republic of, Peru, Philippines, Poland, Russian Federation, Saudi Arabia, Spain, Taiwan, Thailand, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed