Phase 2, Single-arm, Open-label Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer with Actionable Genomic Alterations and Progressed On or After Applicable Targeted Therapy and Platinum-based Chemotherapy (TROPION-Lung05)
- Conditions
- Non-Small cell Lung CancerNSCLC10029107
- Registration Number
- NL-OMON51908
- Lead Sponsor
- Daiichi Sankyo, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 13
Has pathologically documented NSCLC that
• Is stage IIIB, IIIC or stage IV NSCLC disease at the time of enrollment
(based on the American
Joint Committee on Cancer, Eighth Edition).
• Has 1 or more of the following documented activating genomic alterations*:
EGFR**, ALK,
ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.
* KRAS mutations in the absence of any of the genomic alterations specified
above will be
excluded.
** Overexpression of EGFR, in the absence of activating mutations, is NOT
sufficient for
enrollment. Subjects who have not received osimertinib should be evaluated for
the presence of
EGFR T790M mutation after relapse/progression on/after the most recent EGFR
tyrosine kinase
inhibitor (TKI), unless the subject is already known to be positive with
documented results for
this mutation or unless osimertinib is not locally approved.
• Has documentation of radiographic disease progression while on or after
receiving the most recent
treatment regimen for advanced or metastatic NSCLC.
• Subject must meet the following for advanced or metastatic NSCLC:
• Has been treated with at least 1 but no more than 2 cytotoxic
agent-containing therapy in
the metastatic setting:
* One platinum-containing regimen (either as monotherapy or combination
therapy);
* May have received up to one additional line of cytotoxic agent-containing
therapy;
* Those who received a platinum-containing regimen as adjuvant therapy for
early stage
disease must have relapsed or progressed while on the treatment or within 6
months of the
last dose OR received at least one additional course of platinum-containing
therapy (which
may or may not be same as in the adjuvant setting) for relapsed/progressive
disease;
• May have received up to one checkpoint inhibitor (CPI)-containing regimen
(may be in
combination with a cytotoxic agent as part of a regimen described above or as
an additional CPI
regimen without a cytotoxic agent);
• Has been treated with 1 or more lines of non-CPI targeted therapy that is
locally approved for
the subject*s applicable genomic alteration at the time of screening; OR one or
more of the
agents specified in the table below;
* Those who received a targeted agent for the applicable genomic alterations
in the study as
adjuvant therapy for early stage disease must have relapsed or progressed while
on the
treatment or within 6 months of the last dose OR received at least one
additional course of
targeted therapy for the same genomic alterations (which may or may not be same
agent
used in the adjuvant setting) for relapsed/progressive disease.
* Subjects who have been treated with a prior TKI must receive additional
targeted therapy,
if clinically appropriate, for the genomic alterations that are considered
amenable or the
subject will not be allowed in the study.
• Must undergo a mandatory pre-treatment tumor biopsy procedure.
OR
• If available, a tumor biopsy that was recently collected (within 3 months of
screening) after
completion of the most recent anticancer treatment regimen and that has a
minimum of
10 × 4 micron sections or a tissue block equivalent of 10 × 4 micron sections
may be substituted for
the mandatory biopsy collected during screening.
Note: Results from this biopsy will not be used to deter
1. 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 weeks must have elapsed between the end of whole brain
radiotherapy and study enrollment. Note: A computed tomography (CT) or magnetic
resonance imaging (MRI) scan of the brain at baseline is required for all
subjects. For those subjects in whom central nervous system (CNS) metastases
are first discovered at the time of screening, the treating investigator should
consider delay of study treatment to document stability of CNS metastases with
repeat imaging at least 4 weeks later (in which case, repeat of all screening
activity may be required).
2. Has leptomeningeal carcinomatosis.
3. Had prior treatment with:
a. Any chemotherapeutic agent targeting topoisomerase I, including antibody
drug conjugate
(ADC) containing such agent.
b. TROP2-targeted therapy.
4. Uncontrolled or significant cardiovascular disease, including:
a. Mean QT interval corrected for heart rate using Fridericia*s formula (QTcF)
>470 milliseconds (msec) (based on the average of screening triplicate 12-lead
electrocardiogram determinations).
b. History of myocardial infarction within 6 months prior to Cycle 1 Day 1.
c. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day
1.
d. Symptomatic congestive heart failure (CHF) (New York Heart Association Class
II to IV) at screening. Subjects with a history of Class II to IV CHF prior to
screening must have returned to Class I CHF and have LVEF >=50% (by either an
ECHO or MUGA scan within 28 days of Cycle 1 Day 1) in order to be eligible.
e. History of serious cardiac arrhythmia requiring treatment.
f. LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan.
g. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or
diastolic blood pressure >110 mmHg).
5. 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.
6. Clinically severe pulmonary compromise resulting from intercurrent pulmonary
illnesses including, but not limited to, any underlying pulmonary disorder (ie,
pulmonary emboli within 3 months of Cycle 1 Day 1, severe asthma, severe
chronic obstructive pulmonary disease, restrictive lung disease, pleural
effusion, etc.), or any autoimmune, connective tissue or inflammatory disorders
with pulmonary involvement (ie, rheumatoid arthritis, Sjögren's syndrome,
sarcoidosis, etc.), or prior pneumonectomy.
7 Clinically significant corneal disease.
8. Has other primary malignancies, except adequately resected non-melanoma skin
cancer, curatively treated in situ disease, or other solid tumors curatively
treated, with no evidence of disease for >=3 years.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>ORR as assessed by BICR per RECIST v1.1.</p><br>
- Secondary Outcome Measures
Name Time Method <p>DoR, SoD, DCR, CBR, PFS, TTR as assessed by BICR and by investigator per RECIST<br /><br>v1.1.<br /><br>ORR as assessed by investigator per RECIST v1.1.<br /><br>OS.<br /><br><br /><br>Descriptive statistics of safety endpoints.<br /><br>Plasma concentrations and PK parameters of DS-1062a, total anti- TROP2<br /><br>antibody, and MAAA-1181a.<br /><br>Prevalence and incidence of ADA. </p><br>