The primary purpose of the study is to assess the safety, tolerability, and anti-tumor activity of HER3-DXd and T-DXd in the combination dosing regimens in participants with hormone receptor positive, HER2-low or HER2-ultralow, unresectable, or metastatic breast cancer.
Unresectable or metastatic.
HR+ based on testing performed locally. HR+ (estrogen receptor [ER] and/or progesterone receptor [PgR] positive [ER or PgR greater than equal to (≥)1 percent (%)] per American Society of Clinical Oncology [ASCO]/College of American Pathologists [CAP] 2020 guidelines) in the unresectable or metastatic setting.
Assessed as HER2-low (defined as Immunohistochemistry (IHC)2+/In-situ hybridization (ISH)- or IHC1+) or HER2-ultralow (defined as IHC 0 with any membrane staining in greater than (>) 0 and lesser than equal to (≤)10% of the cancer cells) locally for Part 1 and centrally for Part 2. The HER2 result must be from a tumor sample obtained in the unresectable or metastatic setting.
For Dose Regimen Determination (Part 1), HER2 status used for eligibility assessment must be determined locally (according to applicable regulations) using the PATHWAY anti-HER2/neu (4B5) Rabbit Monoclonal Primary Antibody (Ventana Medical Systems, Inc.). Additional HER2 testing will be performed locally and according to applicable regulations using the prescribed test during Screening only if prior results obtained with this test are not available for eligibility assessment.
Prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate (ADC) that consists of a topoisomerase I inhibitor (e.g., T-DXd) or any other topoisomerase I inhibitor therapy.
Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at Screening. Examples of suspected ILD/pneumonitis by imaging include the presence of lung parenchymal fibrosis, such as CPFE, and any radiographic features consistent with ILA, including but not limited to, extensive ground glass opacities, reticular opacities, traction bronchiectasis, and honeycombing. Participants may be eligible if they had history of radiation pneumonitis that did not require steroids.
Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone daily or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to randomization. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the trial.
Evidence of spinal cord compression or brain metastases, defined as being clinically active and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive or treated brain metastases who are asymptomatic (i.e., without neurologic signs or symptoms and do not require treatment with corticosteroids or anticonvulsants) may be included in the trial but must have a stable neurologic status for ≥4 weeks prior to Cycle 1 Day 1. Participants with asymptomatic brain metastases and treated with anticonvulsants as prophylaxis can enroll.
Parallel
Patritumab deruxtecan
DrugIntravenous administration as determined by treatment arm.
Trastuzumab deruxtecan
DrugIntravenous administration as determined by treatment arm.
Part 1: Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Adverse event(AE): any untoward medical occurrence in a participant administered pharmaceutical product (PP) and which does not necessarily have a causal relationship with the treatment.AE can therefore be any unfavorable and unintended sign(including an abnormal laboratory finding, for example),symptom,or disease temporally associated with the use of PP, whether or not considered related to the PP.Pre-existing conditions which worsen during study are also considered as AEs.SAE:any AE that fulfilled any of following criteria:fatal,life-threatening,required inpatient hospitalisation or prolongation of existing hospitalization,resulted in persistent or significant disability/incapacity,was congenital anomaly/birth defect, medically significant or required intervention to prevent any of the other outcomes listed here. TEAEs:AEs with start or worsening date during the on-treatment period(from 1st dose date of trial intervention to 47 days after the last dose date of trial intervention).
Part 2: Objective Response Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v.1.1) as Assessed by the Investigator
Objective response is defined as participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as assessed by investigator per RECIST v1.1.
Part 1: Objective Response Per RECIST v.1.1 as Assessed by the Investigator
Objective response is defined as participants with a BOR of confirmed CR or confirmed PR, as assessed by investigator per RECIST v1.1.
Part 2: Number of Participants With at Least One TEAE and SAE
AE: any untoward medical occurrence in a participant administered pharmaceutical product (PP) and which does not necessarily have a causal relationship with the treatment.AE can therefore be any unfavorable and unintended sign(including an abnormal laboratory finding, for example),symptom,or disease temporally associated with the use of PP, whether or not considered related to the PP.Pre-existing conditions which worsen during study are also considered as AEs.SAE:any AE that fulfilled any of following criteria:fatal,life-threatening,required inpatient hospitalisation or prolongation of existing hospitalization,resulted in persistent or significant disability/incapacity,was congenital anomaly/birth defect, medically significant or required intervention to prevent any of the other outcomes listed here. TEAEs:AEs with start or worsening date during the on-treatment period(from 1st dose date of trial intervention to 47 days after the last dose date of trial intervention).
Parts 1 and 2: Disease Control Per RECIST v.1.1 as Assessed by the Investigator
Disease control is defined as participants with a BOR of confirmed CR, confirmed PR, or SD per RECIST v1.1.
Parts 1 and 2: Duration of Response (DoR) Per RECIST v.1.1 as Assessed by the Investigator
DoR is defined as the time (month) from date of initial response (CR or PR) to the earlier date of the first objective documentation of radiographic disease progression or death due to any cause.
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Daiichi Sankyo
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
