Trial Title:
DS8201a and Pembrolizumab in Participants With Locally Advanced/Metastatic Breast or Non-Small Cell Lung Cancer
NCT ID:
NCT04042701
Condition:
Breast Cancer
Non-small Cell Lung Carcinoma
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Pembrolizumab
Trastuzumab
Camptothecin
Trastuzumab deruxtecan
Immunoconjugates
Conditions: Keywords:
Human epidermal receptor 2 positive
Human epidermal receptor 2
Non-small Cell Lung Carcinoma
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Phase 1b, open-label, 2-part, multicenter, non-randomized, multiple-dose study
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Trastuzumab deruxtecan (DS-8201a)
Description:
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.
Arm group label:
HER2-expressing NSCLC (Part 2 Dose Expansion)
Arm group label:
HER2-low breast cancer (Part 2 Dose Expansion)
Arm group label:
HER2-mutant NSCLC (Part 2 Dose Expansion)
Arm group label:
HER2-positive breast cancer (Part 2 Dose Expansion)
Intervention type:
Drug
Intervention name:
Trastuzumab deruxtecan (DS-8201a)
Description:
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.
Arm group label:
Part 1 (Dose Escalation)
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
All participants will receive pembrolizumab (200 mg Q3W) via intravenous (IV) infusion
prior to DS-8201a in Parts 1 and 2 of the study.
Arm group label:
HER2-expressing NSCLC (Part 2 Dose Expansion)
Arm group label:
HER2-low breast cancer (Part 2 Dose Expansion)
Arm group label:
HER2-mutant NSCLC (Part 2 Dose Expansion)
Arm group label:
HER2-positive breast cancer (Part 2 Dose Expansion)
Arm group label:
Part 1 (Dose Escalation)
Other name:
KEYTRUDA®
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.
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.
Criteria for eligibility:
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 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
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Univ. of Cali. San Francisco Medical Center
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Yale Cancer Center
Address:
City:
New Haven
Zip:
06520
Country:
United States
Status:
Completed
Facility:
Name:
Cancer Specialists of North Florida (Cbo)
Address:
City:
Jacksonville
Zip:
32256
Country:
United States
Status:
Recruiting
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
32256
Country:
United States
Status:
Recruiting
Facility:
Name:
Moffit Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Center for Cancer & Blood Disorders
Address:
City:
Bethesda
Zip:
20817
Country:
United States
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Massachusetts General Hospital Cancer Center
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Completed
Facility:
Name:
Siteman Cancer Center-Washington University
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Completed
Facility:
Name:
Fox Chase Cancer Center
Address:
City:
Philadelphia
Zip:
19111
Country:
United States
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Hope Cancer Center of East Texas
Address:
City:
Tyler
Zip:
75701
Country:
United States
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Institut Bergonie
Address:
City:
Bordeaux
Zip:
33000
Country:
France
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Centre Hospitalier Intercommunal de Créteil
Address:
City:
Créteil
Zip:
94000
Country:
France
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
CHUTimone
Address:
City:
Marseille
Zip:
13385
Country:
France
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Institut PAOLI-CALMETTES
Address:
City:
Marsielle
Zip:
13273
Country:
France
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
CHU de Poitiers
Address:
City:
Poitiers
Zip:
86000
Country:
France
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Univ. du Cancer de Toulouse
Address:
City:
Toulouse
Zip:
31100
Country:
France
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Institut Gustave Roussy
Address:
City:
Villejuif
Zip:
94805
Country:
France
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Hospital Teresa Herrera (C.H.U.A.C)
Address:
City:
A Coruña
Zip:
15006
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Inst. Oncologico Baselga Hospital Quiron
Address:
City:
Barcelona
Zip:
08023
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Hospital de la Santa Creu i de Sant Pau
Address:
City:
Barcelona
Zip:
08025
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Hopital Universitario Insular de Gran Canaria
Address:
City:
Las Palmas de Gran Canaria
Zip:
35016
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital General Univ. Gregorio Marañon
Address:
City:
Madrid
Zip:
28009
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Madrid
Zip:
28033
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Hospital Universitario Virgen Macarena
Address:
City:
Sevilla
Zip:
41009
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Hospital Universitario Miguel Servet
Address:
City:
Zaragoza
Zip:
50009
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
The Royal Marsden NHS Foundation Trust
Address:
City:
London
Zip:
SW3 6JJ
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Sarah Cannon Research Institute (SCRI)
Address:
City:
London
Zip:
W1G 6AD
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
The Christie NHS Fond. Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Royal Marsden Hosptial
Address:
City:
Sutton
Zip:
SM2 5PT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Principal Investigator
Facility:
Name:
Clatterbridge Cancer Centre
Address:
City:
Wirral
Zip:
CH63 4JY
Country:
United Kingdom
Status:
Withdrawn
Start date:
February 10, 2020
Completion date:
August 1, 2025
Lead sponsor:
Agency:
Daiichi Sankyo
Agency class:
Industry
Collaborator:
Agency:
AstraZeneca UK Limited
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Daiichi Sankyo
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT04042701
