DS8201a and Pembrolizumab in Participants With Locally Advanced/Metastatic Breast or Non-Small Cell Lung Cancer

Running, not enrolling · Phase 1

Conditions studied: Breast Cancer, Non-small Cell Lung Carcinoma

In brief

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.

Key facts

Study ID: NCT04042701
Run by: Daiichi Sankyo
People needed: 115
Starts: 2020-02-10
Expected to finish: 2027-03-31
Last updated by the study team: 2025-11-18

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Written informed consent
Adults ≥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) ≥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 or locally 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

You may not qualify if…

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

Where it is running

Univ. of Cali. San Francisco Medical Center — San Francisco, California, United States
Yale Cancer Center — New Haven, Connecticut, United States
Cancer Specialists of North Florida (Cbo) — Jacksonville, Florida, United States
Moffitt Cancer Center — Tampa, Florida, United States
Moffit Cancer Center — Tampa, Florida, United States
Center for Cancer & Blood Disorders — Bethesda, Maryland, United States
Massachusetts General Hospital Cancer Center — Boston, Massachusetts, United States
Siteman Cancer Center-Washington University — St Louis, Missouri, United States
Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States
Hope Cancer Center of East Texas — Tyler, Texas, United States
Institut Bergonie — Bordeaux, France
Centre Hospitalier Intercommunal de Créteil — Créteil, France
CHUTimone — Marseille, France
Institut PAOLI-CALMETTES — Marsielle, France
CHU de Poitiers — Poitiers, France
Univ. du Cancer de Toulouse — Toulouse, France
Institut Gustave Roussy — Villejuif, France
Hospital Teresa Herrera (C.H.U.A.C) — A Coruña, Spain
Inst. Oncologico Baselga Hospital Quiron — Barcelona, Spain
Hospital de la Santa Creu i de Sant Pau — Barcelona, Spain
Hopital Universitario Insular de Gran Canaria — Las Palmas de Gran Canaria, Spain
Hospital General Univ. Gregorio Marañon — Madrid, Spain
MD Anderson Cancer Center — Madrid, Spain
Hospital Universitario 12 de Octubre — Madrid, Spain
Hospital Universitario Virgen Macarena — Seville, Spain

Full record on ClinicalTrials.gov

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