A Phase 2, Multicenter, Randomized Study of Trastuzumab deruxtecan in Subjects With HER2-Mutated Metastatic Non-Small Cell Lung Cancer (NSCLC) [Destiny-Lung02]
- Conditions
- HER-2 Mutated Metastatic Non-Small Cell Lung CancerLung Cancer10029107
- Registration Number
- NL-OMON54233
- Lead Sponsor
- Daiichi Sankyo Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 11
1. Must have provided informed consent for study participation (see Section
10.1.2 of the protocol) before performance of any study-specific procedure or
test.
2. Men or women >=18 years old. (Please follow local regulatory requirements if
the legal age of
consent for study participation is >18 years old).
3. Pathologically documented metastatic NSCLC with a known activating HER2
mutation
(please refer to the list of HER2 mutations, see Table 10.2 of the protocol).
The HER2 mutation must be documented from an archival or fresh tumor tissue
sample analyzed by Clinical Laboratory
Improvement Amendments (CLIA) certified laboratory or equivalent laboratory
performing
testing to Good Laboratory Practice (GLP) standard.
Note: HER2 mutation documented only from a liquid biopsy sample cannot be used
for
enrollment.
4. Subjects who had previous treatment including platinum therapy in the
metastatic/locally advanced setting and not amenable to curative surgery or
radiation. The subject must have progressed during or after the last treatment
regimen or discontinued because of unacceptable toxicity.
5. Presence of at least 1 measurable lesion confirmed by BICR based on RECIST
version 1.1.
6. Is willing and able to provide an adequate archival tumor tissue sample. A
fresh biopsy is
required if an archival tumor tissue sample cannot be supplied. Resection and
core needle biopsy are acceptable. Other tissue samples, eg, fine needle
aspirates or cell block are not
acceptable. For detailed instruction on tissue submission, please refer to the
laboratory manual.
7. Has ECOG PS of 0 to 1.
8. Has left ventricular ejection fraction (LVEF) >= 50% within 28 days before
randomization.
9. Has adequate organ function within 14 days before randomization (please
refer to additional information in the protocol, paragraph 5.1).
10. Has adequate treatment washout period before randomization (please refer to
additional information in the protocol, paragraph 5.1)
11. Male and female subjects of reproductive/childbearing potential must agree
to use a highly
effective form of contraception or avoid intercourse during and upon completion
of the study
and for at least 7 months for females and 4 months for males, after the last
dose of study drug.
Methods considered as highly effective methods of contraception are described
in Section 5.1 of the protocol.
12. Male subjects must not freeze or donate sperm starting at randomization and
throughout the study period, and at least 4 months after the final study drug
administration. Preservation of sperm
should be considered prior to randomization in this study.
13. Female subjects must not donate, or retrieve for their own use, ova from
the time of randomization and throughout the study treatment period, and for at
least 7 months after the final study drug administration. Female subjects must
refrain from breastfeeding throughout this time. Preservation of ova may be
considered prior to randomization in this study.
14. Life expectancy of 3 months or more.
Please refer to protocol for complete list of inclusion criteria.
Has a known driver mutation in the epidermal growth factor receptor (EGFR),
BRAF or MET exon 14 gene or a known anaplastic lymphoma kinase (ALK), ROS1, RET
or NTRK fusion.
2. Medical history of myocardial infarction within 6 months before
randomization, symptomatic
congestive heart failure (CHF) (New York Heart Association Class II to IV.
Subjects with
troponin levels above ULN at screening (as defined by the manufacturer), and
without any MI
related symptoms should have a cardiologic consultation before randomization to
rule out MI.
3. Has a corrected QT interval (QTcF) prolongation > 470 msec (females) or >450
msec (males)
based on average of triplicate12-lead ECG at screening.
4. Has a history of (non-infectious) ILD/pneumonitis that required steroids,
has current
ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by
imaging at
screening.
5. 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 brain radiotherapy and study
randomization.
6. Has multiple primary malignancies within 3 years, except adequately resected
non-melanoma
skin cancer, curatively treated in-situ disease, or other solid tumors
curatively treated.
7. Has a history of severe hypersensitivity reactions to either the drug
substances or inactive
ingredients in the drug product.
8. Has a history of severe hypersensitivity reactions to other monoclonal
antibodies.
9. Has an uncontrolled infection requiring intravenous (IV) antibiotics,
antivirals, or antifungals.
10. Has substance abuse or any other medical conditions such as clinically
significant cardiac or
psychological conditions, that may, in the opinion of the investigator,
interfere with the
subject*s participation in the clinical study or evaluation of the clinical
study results.
11. Known human immunodeficiency virus (HIV) infection. Subjects should be
tested for HIV
prior to randomization if required by local regulations or institutional review
board (IRB)/
independent ethics committee (IEC).
12. Known active clinically relevant liver disease (eg, active hepatitis B, or
active hepatitis C), such as those with serologic evidence of viral infection
within 28 days of Cycle 1, Day 1. Subjects with past or resolved hepatitis B
virus (HBV) infection are eligible, if negative for hepatitis B surface antigen
(HBsAg[-]) and positive for hepatitis B core antibody (anti-HBc[+]). Subjects
positive for hepatitis C (HCV) antibody are eligible only if the polymerase
chain reaction is negative for HCV RNA.
13. Unresolved toxicities from previous anticancer therapy, defined as
toxicities (other than
alopecia) not yet resolved to Grade <= 1 or baseline. Note: Subjects may be
enrolled with
chronic Grade 2 toxicities (defined as no worsening to > Grade
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint is confirmed ORR, defined as the proportion of<br /><br>subjects with CR or PR, assessed by the blinded independent<br /><br>central review (BICR) based on RECIST version 1.1</p><br>
- Secondary Outcome Measures
Name Time Method