Trastuzumab deruxtecan for HER2-positive metastatic breast cancer

Inclusion criteria

• {"criterion_text":"- Patients must be at least 18 years of age\n- 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\n- Patient must have adequate tumor sample from the metastatic setting for biomarker assessment\n- ECOG Performance Status of 0 or 1\n- 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.\n- Part 2 (Modules 0 - 5) a) No prior lines of therapy for advanced/MBC allowed\n- Part 2 (Module 6 and 7) a) Zero or one prior lines of therapy for advanced/MBC allowed CNS Inclusion\n- 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"}

Exclusion criteria

• {"criterion_text":"- Uncontrolled or significant cardiovascular disease\n- Active or prior documented (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening\n- Lung-specific intercurrent clinically significant illnesses\n- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals\n- Spinal cord compression or a history of leptomeningeal carcinomatosis\n- Prior treatment with immune checkpoint inhibitors\n- Prior treatment with an ADC containing a topoisomerase I inhibitor\n- Prior treatment with tucatinib\n- 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"}

Primary endpoints

• {"endpoint_text":"- Part 1: AEs, SAEs, DLTs, laboratory findings\n- Part 2: AEs, SAEs, laboratory findings","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"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."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"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."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"PFS2 is defined as time from the date of randomisation until the date of progression on next line treatment or death; second progression defined per local standard clinical practice."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"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."}
• {"endpoint_text":"- Part 2: OS is defined as time from the date of randomisation until the date of death due to any cause.","definition_or_measurement_approach":"OS is defined as time from the date of randomisation until the date of death due to any cause."}
• {"endpoint_text":"- Serum concentration of T-DXd, total anti-HER2 antibody, MAAA- 1181a, durvalumab, and pertuzumab; plasma concentration of paclitaxel and tucatinib","definition_or_measurement_approach":"Measurement of serum/plasma concentrations of listed agents (PK endpoints) as specified in protocol pharmacokinetic assessments."}
• {"endpoint_text":"- Immunogenicity for T-DXd, durvalumab, and pertuzumab","definition_or_measurement_approach":"Assessment of immunogenicity (anti-drug antibodies) for T-DXd, durvalumab, and pertuzumab as per protocol immunogenicity assays."}

Spain

Latest Decision Or Authorization Date

17-06-2024

Number Of Sites

4

Number Of Participants

23

Poland

Latest Decision Or Authorization Date

17-06-2024

Number Of Sites

2

Number Of Participants

6

Germany

Latest Decision Or Authorization Date

13-06-2024

Number Of Sites

1

Number Of Participants

1

Italy

Latest Decision Or Authorization Date

17-06-2024

Number Of Sites

4

Number Of Participants

16

Primary sponsor

Full Name

AstraZeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden