A PHASE 2, MULTICENTER, OPEN-LABEL, 2-COHORT STUDY OF TRASTUZUMAB DERUXTECAN (DS-8201a), AN ANTI-HER2 ANTIBODY DRUG CONJUGATE (ADC), FOR HER2-OVER-EXPRESSING OR -MUTATED, UNRESECTABLE AND/OR METASTATIC NONSMALL CELL LUNG CANCER (NSCLC)
- Conditions
- Lung CanerMetastatic Non-Small Cell Lung Cancer10038666
- Registration Number
- NL-OMON54783
- Lead Sponsor
- DAIICHI SANKYO, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 31
1. Must have provided informed consent for study participation (see Section
15.3) before performance of any study-specific procedure or test.
2. Age >=20 y old in Japan, >=18 y old in other countries.
3. Pathologically documented unresectable and/or metastatic nonsquamous NSCLC.
4. Has relapsed from or is refractory to standard treatment or for which no
standard treatment is available.
5. For Cohort 1 and Cohort 1a only: HER2-overexpression (IHC 2+ or 3+) status
must be assessed and confirmed by Clinical Laboratory Improvement Amendments
(CLIA)-certified laboratory or equivalent, from an archival tumor tissue sample.
For Cohort 2 only: Documented any known activating HER2 mutation from an
archival tumor tissue sample analyzed by CLIA laboratory or equivalent,
specifically exon 20 insYVMA (Y772_A775dup), insGSP (G778_P780dup), insTGT
(G776delinsVC), single base pair substitutions
L755S, V777L, or S310F or another HER2 mutation listed in the appendix (see
Section 17.7). Note: HER2 mutation documented only from a liquid biopsy sample
cannot be used for enrollment.
6. Presence of at least 1 measurable lesion assessed by the investigator based
on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
7. Is willing and able to provide an adequate archival tumor tissue sample.
Fine needle aspirates are not acceptable
8. Is willing to undergo a tissue biopsy, after the completion of the most
recent treatment regimen.
9. Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to
1.
1. Previously treated with HER2-targeted therapies, except for pan-HER class
tyrosine kinase inhibitors. 2. For Cohort 1 and Cohort 1a only: Has known HER2
mutation. 3. Uncontrolled or significant cardiovascular disease, including any
of the following: a. Medical history of myocardial infarction within 6 months
prior to enrollment b. Symptomatic congestive heart failure (CHF) (New York
Heart Association Class II to IV) 28 d prior to enrollment c. Troponin levels
consistent with myocardial infarction (as defined by the manufacturer) 28 d
prior to enrollment d. History of unstable angina, or serious cardiac
arrhythmia requiring treatment e. Left ventricular ejection fraction (LVEF) <
50% within 28 d prior to enrollment f. Has a corrected QT interval (QTcF)
prolongation to > 470 ms (females) or >450 ms (males) based on average of the
screening triplicate12-lead electrocardiogram (ECG). 4. Has a 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. 5. Has clinically significant
corneal disease in the opinion of the Investigator. 6. Has spinal cord
compression or clinically active central nervous system metastases, defined as
untreated and symptomatic, or requiring therapy with corticosteroids or
anticonvulsants to control associated symptoms. Subjects with clinically
inactive brain metastases may be included in the study. Subjects with treated
brain metastases that are no longer symptomatic and who require no treatment
with corticosteroids or anticonvulsants may be included in the study if they
have recovered from the acute toxic effect of radiotherapy. A minimum of 2 wk
must have elapsed between the end of whole brain radiotherapy and study
enrollment. 7. Has multiple primary malignancies within 3 y, except adequately
resected non-melanoma skin cancer, curatively treated in-situ disease, or other
solid tumors curatively treated.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Efficacy Endpoint:<br /><br>The primary efficacy endpoint (primary outcome measure) is ORR assessed by<br /><br>independent central review (ICR) based on RECIST version 1.1 for each cohort.</p><br>
- Secondary Outcome Measures
Name Time Method