HER2-positive Metastatic Breast Cancer MedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria: -Patients must be at least 18 years of age - Pathologically documented breast cancer that: a) Is advanced/unresectable (patients that can be treated with curative intent are not eligible) or metastatic b) HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local assessment. The local HER2 result must be from a tumour sample obtained in the metastatic setting. c) Is documented as hormone receptor-positive (estrogen or progesterone receptor) or negative in the metastatic setting -Patient must have adequate tumor sample from the metastatic setting for biomarker assessment -ECOG Performance Status of 0 or 1 -Part 1 a) Disease progression on or after the last systemic therapy prior to starting study treatment b) At least 1 prior treatment line in metastatic setting required. -Part 2 (Modules 0 - 5) a) No prior lines of therapy for advanced/MBC allowed -Part 2 (Module 6 and 7) a) Zero or one prior lines of therapy for advanced/MBC allowed CNS Inclusion -Modules 0 - 5 Patients must have no brain metastases or stable brain metastases. -Module 6 and 7 Patients must have untreated brain metastases not needing local therapy or previously treated brain metastases that have progressed since prior local therapy 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 405 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: -Uncontrolled or significant cardiovascular disease -Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening -Lung-specific intercurrent clinically significant illnesses -Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals -Spinal cord compression or a history of leptomeningeal carcinomatosis -Prior treatment with immune checkpoint inhibitors -Prior treatment with an ADC containing a topoisomerase I inhibitor -Prior treatment with tucatinib CNS Exclusion -Modules 0 - 5: Has untreated brain metastasis -Module 6 and 7: Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg dexamethasone or any brain lesion thought to require immediate local therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study is modular in design allowing assessment of safety, tolerability and anti-tumour activity of T-DXd in combination with other anti-cancer agents. Combination-treatment modules will have 2 parts: a dose-finding phase (Part 1), and a dose expansion phase (Part 2); the recommended Phase 2 dose (RP2D) determined in Part 1 will be used for the dose-expansion in Part 2. The target population of interest in this study is patients with HER2-positive (as per ASCO/CAP 2018 guidelines) advanced/MBC. Part 1 of each module will enroll patients with locally assessed HER2-positive advanced/MBC in second-line or later patients. Part 2 of each module will enroll patients with locally assessed HER2-positive breast cancer who have not received prior treatment for advanced/metastatic disease. Part 1: To assess the safety and tolerability, and determine RP2D for the T-DXd combinations Part 2: To assess the safety and tolerability of T-DXd monotherapy and T-DXd combinations;Secondary Objective: Part 1 and Part 2: To assess anti-tumour activity of T-DXd combinations and T-DXd monotherapy Part 1 and Part 2: To assess the PK of T-DXd, durvalumab, pertuzumab, paclitaxel, and tucatinib, and investigate the immunogenicity of T-DXd, durvalumab, and pertuzumab;Primary end point(s): Part 1: AEs, SAEs, DLTs, laboratory findings Part 2: AEs, SAEs, laboratory findings;Timepoint(s) of evaluation of this end point: Safety will be assessed up to the follow-up period, approximately 53 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Part 1 and Part 2: ORR is defined as the proportion of patients who have a CR or PR, as determined by the Investigator at local site per RECIST 1.1. 2. Part 1 and Part 2: PFS is defined as time from the date of randomisation until the date of progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause. 3. Part 2: PFS2 is defined as time from the date of randomisation until the date of progression on next line treatment (the earliest of the progression event subsequent to first subsequent anticancer therapy) or death; second progression will be defined according to local standard clinical practice. 4. Part 2: DoR is defined as time from the date of first documented response until the date of documented progression or death in the absence of disease progression. 5. Part 2: OS is defined as time from the date of randomisation until the date of death due to any cause. 6. Serum concentration of T-DXd, total anti-HER2 antibody, MAAA-1181a, durvalumab, and pertuzumab; plasma concentration of paclitaxel and tucatinib 7. Immunogenicity for T-DXd, durvalumab, and pertuzumab;Timepoint(s) of evaluation of this end point: 1. Until progression, assessed up to approximately 53 months 2. Until progression, assessed up to approximately 53 months 3. Assessed up to approximately 53 months 4. Until progression, assessed up to approximately 53 months 5. Until death, assessed up to approximately 53 months 6. While on study drug up to study completion, approximately 53 months 7. Up to follow-up period, approximately 53 months | — |
Countries
Australia, Brazil, Canada, France, Germany, India, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, Türkiye, United Kingdom, United States
Contacts
Public ContactClinical Study Information Center
AstraZeneca
Outcome results
None listed