Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    ds8201-a-u106
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04042701
Recruitment Status : Recruiting
First Posted : August 2, 2019
Last Update Posted : April 30, 2021
Sponsor:
Collaborators:
AstraZeneca UK Limited
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Breast Cancer Non-small Cell Lung Carcinoma Drug: Trastuzumab deruxtecan (DS-8201a) Drug: Pembrolizumab Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 115 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase 1b, open-label, 2-part, multicenter, non-randomized, multiple-dose study
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 10, 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1 (Dose Escalation)
HER2-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.
Drug: Trastuzumab deruxtecan (DS-8201a)

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.


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

Experimental: HER2-positive breast cancer (Part 2 Dose Expansion)
HER2-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.
Drug: Trastuzumab deruxtecan (DS-8201a)

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.


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

Experimental: HER2-low breast cancer (Part 2 Dose Expansion)
HER2 low breast cancer participants with prior failed standard treatments who received DS8201a at the RDE in combination with pembrolizumab 200 mg.
Drug: Trastuzumab deruxtecan (DS-8201a)

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.


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

Experimental: HER2-expressing NSCLC (Part 2 Dose Expansion)
HER2-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.
Drug: Trastuzumab deruxtecan (DS-8201a)

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.


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

Experimental: HER2-mutant NSCLC (Part 2 Dose Expansion)
HER2-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.
Drug: Trastuzumab deruxtecan (DS-8201a)

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.


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




Primary Outcome Measures :
  1. Dose-limiting toxicities (DLTs), Part 1 [ Time Frame: Within two 3-week cycles (6 weeks) ]
    Maximum Tolerated Dose (MTD) or recommended dose expansion (RDE) of DS-8201a (Part1) are based on the occurrence of DLTs.

  2. Objective Response Rate (ORR), Confirmed by Independent Central Review, Part 2 [ Time Frame: Within approximately 30 months ]

Secondary Outcome Measures :
  1. Treatment-emergent adverse events [ Time Frame: Within approximately 30 months ]
  2. Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) [ Time Frame: 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) ]
    Cmax of trastuzumab deruxtecan, MAAA-118A, and total anti-HER2 antibody will be assessed.

  3. Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC) [ Time Frame: 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) ]
    Area under the concentration-time curve of trastuzumab deruxtecan, MAAA-118A, and total anti-HER2 antibody will be assessed.

  4. Duration of Response (DoR) [ Time Frame: Within approximately 30 months ]
  5. Disease Control Rate (DCR) [ Time Frame: Within approximately 30 months ]
  6. Progression-Free Survival (PFS), based on Independent Central Review using RECIST v1.1 [ Time Frame: Within approximately 30 months ]
  7. Time to Response (TTR), based on Independent Central Review using RECIST v1.1 [ Time Frame: Within approximately 30 months ]
  8. Overall survival (OS) [ Time Frame: Within approximately 30 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04042701


Contacts
Layout table for location contacts
Contact: Daiichi Sankyo Contact for Clinical Trial Information 908-992-6400 CTRinfo@dsi.com

Locations
Show Show 20 study locations
Sponsors and Collaborators
Daiichi Sankyo, Inc.
AstraZeneca UK Limited
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT04042701    
Other Study ID Numbers: DS8201-A-U106
2018-002489-38 ( EudraCT Number )
KEYNOTE KN-797 ( Other Identifier: Merck Sharp & Dohme Corp )
First Posted: August 2, 2019    Key Record Dates
Last Update Posted: April 30, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) 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 company policies and procedures, Daiichi Sankyo will continue to protect the privacy of 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/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Daiichi Sankyo, Inc.:
Human epidermal receptor 2 positive
Human epidermal receptor 2
Non-small Cell Lung Carcinoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Pembrolizumab
Trastuzumab
Camptothecin
Immunoconjugates
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs