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Breast CancerPhase 1NCT04042701

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

A Phase 1 study testing Trastuzumab deruxtecan (DS-8201a) and Pembrolizumab in people with Breast Cancer and Non-small Cell Lung Carcinoma, run by Daiichi Sankyo at 30 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, Non-small Cell Lung Carcinoma
What is being tested?
Trastuzumab deruxtecan (DS-8201a) and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
115 participants
Where
30 sitesin 4 countries
Study dates
10 Feb 2020to 31 Mar 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Participants in Part 1 should meet the additional inclusion criteria listed for 1 of the 4 cohorts in Part 2.
  • 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
  • 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)
  • 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
  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

30 sites in 4 countries.

30 sites in 4 countries

United States10 sites

  • Center for Cancer & Blood Disorders

    Bethesda, Maryland, 20817

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Cancer Specialists of North Florida (Cbo)

    Jacksonville, Florida, 32256

  • Yale Cancer Center

    New Haven, Connecticut, 06520

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Univ. of Cali. San Francisco Medical Center

    San Francisco, California, 94143

  • Siteman Cancer Center-Washington University

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 32256

  • Moffit Cancer Center

    Tampa, Florida, 33612

  • Hope Cancer Center of East Texas

    Tyler, Texas, 75701

Other trials in United States

Spain9 sites

  • Hospital Teresa Herrera (C.H.U.A.C)

    A Coruña, 15006

  • Inst. Oncologico Baselga Hospital Quiron

    Barcelona, 08023

  • Hospital de la Santa Creu i de Sant Pau

    Barcelona, 08025

  • Hopital Universitario Insular de Gran Canaria

    Las Palmas de Gran Canaria, 35016

  • Hospital General Univ. Gregorio Marañon

    Madrid, 28009

  • MD Anderson Cancer Center

    Madrid, 28033

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Virgen Macarena

    Seville, 41009

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

France7 sites

  • Institut Bergonie

    Bordeaux, 33000

  • Centre Hospitalier Intercommunal de Créteil

    Créteil, 94000

  • CHUTimone

    Marseille, 13385

  • Institut PAOLI-CALMETTES

    Marsielle, 13273

  • CHU de Poitiers

    Poitiers, 86000

  • Univ. du Cancer de Toulouse

    Toulouse, 31100

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

United Kingdom4 sites

  • The Royal Marsden NHS Foundation Trust

    London, SW3 6JJ

  • Sarah Cannon Research Institute (SCRI)

    London, W1G 6AD

  • The Christie NHS Fond. Trust

    Manchester, M20 4BX

  • Royal Marsden Hosptial

    Sutton, SM2 5PT

Other trials in United Kingdom

About this study

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, For Subjects With Locally Advanced/Metastatic Breast Or Non-Small Cell Lung Cancer (NSCLC)

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.

Read the detailed description

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.

Being tested
Trastuzumab deruxtecan (DS-8201a), Pembrolizumab
Keywords
Human epidermal receptor 2 positive, Human epidermal receptor 2, Non-small Cell Lung Carcinoma
Medical subject headings
Breast Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trastuzumab deruxtecan (DS-8201a)Drug

    Part 1: Two dose levels of DS-8201a (3.2 mg/kg Q3W and 5.4 mg/kg Q3W via intravenous (IV) infusion will be administered for the dose escalation part of the study in combination with pembrolizumab.

    Part 2: Once Part 1 of the study is complete and a RDE for DS-8201a has been established, Part 2 will begin. All participants will receive DS-8201a at the RDE in combination with pembrolizumab.

  • Trastuzumab deruxtecan (DS-8201a)Drug

    Part 1: Two dose levels of DS-8201a (3.2 mg/kg Q3W and 5.4 mg/kg Q3W via intravenous (IV) infusion will be administered for the dose escalation part of the study in combination with pembrolizumab.

    Part 2: Once Part 1 of the study is complete and a RDE for DS-8201a has been established, Part 2 will begin.

  • PembrolizumabDrug

    Also called KEYTRUDA®

    All participants will receive pembrolizumab (200 mg Q3W) via intravenous (IV) infusion prior to DS-8201a in Parts 1 and 2 of the study.

Study groups in NCT04042701
Study groupRoleWhat they receive
Part 1 (Dose Escalation)ExperimentalHER2-positive breast cancer, HER2-low expressing breast cancer, HER2-expressing NSCLC, and HER2-mutant NSCLC participants who received escalating doses of DS8201a (initial dose 3.2 mg/kg Q3W) and pembrolizumab 200 mg.
Receives: Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Pembrolizumab
HER2-positive breast cancer (Part 2 Dose Expansion)ExperimentalHER2-positive breast cancer participants with prior ado-trastuzumab emtansine (T-DM1) with disease progression and who received DS8201a at the RDE in combination with pembrolizumab 200 mg.
Receives: Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Pembrolizumab
HER2-low breast cancer (Part 2 Dose Expansion)ExperimentalHER2 low breast cancer participants with prior failed standard treatments who received DS8201a at the RDE in combination with pembrolizumab 200 mg.
Receives: Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Pembrolizumab
HER2-expressing NSCLC (Part 2 Dose Expansion)ExperimentalHER2-expressing NSCLC participants who had not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents and received DS8201a at the RDE in combination with pembrolizumab 200 mg.
Receives: Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Pembrolizumab
HER2-mutant NSCLC (Part 2 Dose Expansion)ExperimentalHER2-mutant NSCLC participants who had not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents and received DS8201a at the RDE in combination with pembrolizumab 200 mg.
Receives: Drug: Trastuzumab deruxtecan (DS-8201a); Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicities (DLTs), Part 1

    Maximum Tolerated Dose (MTD) or recommended dose expansion (RDE) of DS-8201a (Part1) are based on the occurrence of DLTs.

    Measured: Within two 3-week cycles (6 weeks)

  2. Objective Response Rate (ORR), Confirmed by Independent Central Review, Part 2

    Measured: Within approximately 30 months

Secondary outcomes (8)

  1. Treatment-emergent adverse events

    Measured: Within approximately 30 months

  2. Pharmacokinetic Parameter Maximum Serum Concentration (Cmax)

    Cmax of trastuzumab deruxtecan, MAAA-118A, and total anti-HER2 antibody will be assessed.

    Measured: Cycle 1, Day 1: predose and postdose, Day 8, and Day 15; Cycle 2, Day 1 predose and postdose, and Cycle 3, Day 1 (each cycle is 21 days)

  3. Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC)

    Area under the concentration-time curve of trastuzumab deruxtecan, MAAA-118A, and total anti-HER2 antibody will be assessed.

    Measured: Cycle 1, Day 1: predose and postdose, Day 8, and Day 15; Cycle 2, Day 1 predose and postdose, and Cycle 3, Day 1 (each cycle is 21 days)

  4. Duration of Response (DoR)

    Measured: Within approximately 30 months

  5. Disease Control Rate (DCR)

    Measured: Within approximately 30 months

  6. Progression-Free Survival (PFS), based on Independent Central Review using RECIST v1.1

    Measured: Within approximately 30 months

  7. Time to Response (TTR), based on Independent Central Review using RECIST v1.1

    Measured: Within approximately 30 months

  8. Overall survival (OS)

    Measured: Within approximately 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2019
  2. Study start10 Feb 2020
  3. Primary completion21 Jul 2025
  4. Study completion31 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Phase 1b, open-label, 2-part, multicenter, non-randomized, multiple-dose study
Masking
None (open label)
Enrolment
115 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04042701
Sponsor's protocol ID
DS8201-A-U106
Other IDs
2018-002489-38, KEYNOTE-797, MK-3475-797, 2018
Status last verified
Nov 2025
First submitted
31 Jul 2019
Last updated
18 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Trastuzumab deruxtecan (DS-8201a) and Pembrolizumab in people with Breast Cancer and Non-small Cell Lung Carcinoma, run by Daiichi Sankyo at 30 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in United States, Spain, France, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicities (DLTs), Part 1 (time frame: Within two 3-week cycles (6 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04042701.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2025.

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