for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion
Principal Investigator
by Hope Rugo
Photo of Hope Rugo
Hope Rugo



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.

Official Title

A Phase 1b, Multicenter, Two-Part, Open-Label Study of Trastuzumab Deruxtecan (DS-8201a), An Anti-Human Epidermal Growth Factor Receptor-2 (HER2)-Antibody Drug Conjugate (ADC), In Combination With Pembrolizumab, An Anti-PD-1 Antibody, In Subjects With Locally Advanced/Metastatic Breast Or Non-Small Cell Lung Cancer (NSCLC)


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.


Breast Cancer Non-small Cell Lung Carcinoma Human epidermal receptor 2 positive HER2 NSCLC Carcinoma, Non-Small-Cell Lung Pembrolizumab Trastuzumab Camptothecin Immunoconjugates Trastuzumab deruxtecan (DS-8201a)


You can join if…

Open to people ages 18 years and up

  • 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 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 available targeted therapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse standard treatment

You CAN'T join if...

  • Prior treatment with pembrolizumab or DS-8201a
  • Medical history of myocardial infarction within 6 months before enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV), troponin levels consistent with myocardial infarction as defined according to the manufacturer within 28 days prior to enrollment
  • 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
  • Clinically significant corneal disease
  • 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 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
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, contralateral breast cancer, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • 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
  • Uncontrolled infection requiring IV antibiotics, anti-virals, or anti-fungals


  • University of California San Francisco Medical Center accepting new patients
    San Francisco California 94143 United States
  • Fox Chase Cancer Center accepting new patients
    Philadelphia Pennsylvania 19111 United States

Lead Scientist at UCSF

  • Hope Rugo
    Dr. Hope Rugo is a medical oncologist and hematologist specializing in breast cancer research and treatment. A Clinical Professor of Medicine, Dr. Rugo joined the Breast Care Center in 1999 after a decade of experience at UCSF in malignant hematology and bone marrow transplantation for a variety of diseases, including breast cancer.


accepting new patients
Start Date
Completion Date
Daiichi Sankyo, Inc.
Phase 1
Study Type
Last Updated