Breast Cancer Clinical Trial
DS8201a and Pembrolizumab in Participants With Locally Advanced/Metastatic Breast or Non-Small Cell Lung Cancer
This two-part study will include a dose escalation part to determine the recommended dose for expansion of DS8201a and pembrolizumab and a dose expansion part to evaluate efficacy, safety, and tolerability of the combination.
This phase 1b, open-label, 2-part, multicenter, non-randomized, multiple-dose study will evaluate DS-8201a in combination with pembrolizumab in participants with advanced/metastatic breast cancer or non-small cell lung cancer (NSCLC).
In the dose escalation part of the study, escalating doses of DS-8201a in combination with pembrolizumab will be assessed. DS-8201a and pembrolizumab 200 mg will be administered on Day 1 of every 21-day cycle. The initial dose administered for DS8201a will be 3.2 mg/kg Q3W. Escalation to the next dose (5.4 mg/kg Q3W) will be based on acceptable safety signals based on the earlier dose cohort.
Upon completion of dose escalation with the recommended dose of escalation (RDE) established, the dose expansion part of the study will begin. The dose expansion part will include 4 cohorts: Human epidermal growth factor receptor 2 (HER2+) breast cancer participants with prior ado-trastuzumab emtansine (T-DM1), HER2 low breast cancer participants with prior failed standard treatments, HER2-expressing NSCLC participants who have not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents, and HER2-mutant NSCLC participants who have not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents.
Written informed consent
Adults â‰¥18 years
Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1
Pathologically documented HER2-expressing locally advanced/metastatic breast cancer, and HER2-expressing or HER2-mutant locally advanced/metastatic NSCLC
Willing to provide a tumor biopsy during screening and during treatment
Have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator
Adequate cardiac function, as defined by left ventricular ejection fraction (LVEF) â‰¥50% within 28 days before enrollment.
Adequate organ function
Adequate treatment washout period before enrollment
Inclusion Criteria Specific to Part 1
Participants in Part 1 should meet the additional inclusion criteria listed for 1 of the 4 cohorts in Part 2.
Inclusion Criteria Specific to Part 2
Inclusion Criteria for Cohort 1
Pathologically documented, locally advanced/metastatic breast cancer that has centrally determined HER2-positive expression as per American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) Guidelines
Received prior trastuzumab emtansine (T-DM1) therapy with documented progression
Inclusion Criteria for Cohort 2
Pathologically documented, locally advanced/metastatic breast cancer that has centrally determined HER2-low expression (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH-])
Participants must have exhausted treatments that can confer any clinically meaningful benefit (eg, other therapies such as hormonal therapy for participants who are hormone receptor positive)
Inclusion Criteria for Cohort 3
Pathologically documented, locally advanced/metastatic NSCLC that has centrally determined HER2-expression (IHC 1+, 2+, or 3+)
Participants who have known epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK), BRAF V600E mutation, or ROS1 fusion should have disease progression after treatment with at least one genomically-targeted therapy for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment
Inclusion Criteria for Cohort 4
Pathologically documented, locally advanced/metastatic HER2-mutant NSCLC
Participants who have known EGFR mutation, ALK, BRAF V600E mutation, or ROS1 fusion should have disease progression after treatment with at least one genomically-targeted therapy for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment
Prior treatment with pembrolizumab or DS-8201a
Medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal at Screening (as defined by the manufacturer), and without any MI-related symptoms, should have a cardiologic consultation before enrollment to rule out MI
Corrected QT interval (QTc) prolongation to >470 ms (females) or >450 ms (males)
History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
Spinal cord compression or clinically active central nervous system metastases
Active, known or suspected autoimmune disease
Condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment
Prior therapy with an anti-PD-1 or anti-PD-L1 agent
Prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE)
Prior anti-HER2 therapy is not allowed for participants with HER2 low-expressing breast cancer or participants with NSCLC (Cohorts 2, 3, or 4). Prior treatment with pan-HER tyrosine kinase inhibitor is allowed.
Prior systemic anticancer therapy, including investigational agents within 2 to 6 weeks prior to treatment
Unresolved toxicities from previous anticancer therapy
Live vaccine within 30 days prior to the first dose of study drug
Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral breast cancer
History of severe hypersensitivity reactions to other monoclonal antibodies and/or any of the study drug components
Active infection requiring systemic therapy
Known history of human immunodeficiency virus (HIV) infection
Active hepatitis B or C virus infection
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, or any other reason the participant is found not appropriate to participate in the opinion of the treating Investigator
Known psychiatric or substance abuse disorders
Prior organ transplantation, including allogeneic stem cell transplantation
Pregnant, breastfeeding, or planning to become pregnant
Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
Uncontrolled infection requiring IV antibiotics, anti-virals, or anti-fungals
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There are 25 Locations for this study
San Francisco California, 94143, United States More Info
Tampa Florida, 33612, United States More Info
Bethesda Maryland, 20817, United States More Info
Boston Massachusetts, 02114, United States More Info
Saint Louis Missouri, 63110, United States
Philadelphia Pennsylvania, 19111, United States More Info
Tyler Texas, 75701, United States More Info
Bordeaux , 33000, France More Info
CrÃ©teil , 94000, France More Info
Marseille , 13385, France More Info
Marsielle , 13273, France More Info
Poitiers , 86000, France More Info
Toulouse , 31100, France More Info
Villejuif , 94800, France More Info
Barcelona , 08023, Spain More Info
Barcelona , 08025, Spain More Info
Madrid , 28009, Spain More Info
Madrid , 28033, Spain More Info
Madrid , 28041, Spain More Info
Zaragoza , 50009, Spain More Info
London , SW3 6, United Kingdom More Info
London , W1G 6, United Kingdom More Info
Manchester , M20 4, United Kingdom More Info
Sutton , SM2 5, United Kingdom More Info
Wirral , CH63 , United Kingdom
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