A Randomized, Open-label, Phase 3 Trial of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in Treatment-naïve Subjects with Advanced or Metastatic PD-L1 High (TPS >=50%) Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung08)
- Conditions
- 10029211lungcancerNon-Small Cell Lung Cancer
- Registration Number
- NL-OMON55935
- Lead Sponsor
- Daiichi Sankyo, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 15
1. Sign and date the Tissue Screening and Main ICFs, prior to the start of any
study-specific qualification procedures.
2. Adults >=18 years or the minimum legal adult age (whichever is greater) at
the time of informed consent. (Follow local regulatory requirements if the
legal age of adult voluntary consent for study participation is >18 years old.)
3. Histologically documented NSCLC that meets all of the following criteria:
a. Stage IIIB or IIIC disease and not candidates for surgical resection or
definitive chemoradiation, or Stage IV NSCLC disease at the time of
randomization (based on the American Joint Committee on Cancer, Eighth
Edition). Subjects with early-stage NSCLC who have relapsed should be restaged
during screening to ensure their eligibility for the study.
b. Documented negative test results for EGFR, ALK, and ROS1 actionable genomic
alterations based on analysis of tumor tissue. If test results for EGFR, ALK,
and ROS1 are not available, subjects are required to undergo testing performed
locally for these genomic alterations.
c. No known actionable genomic alterations in NTRK, BRAF, RET, MET, or other
actionable driver kinases with locally approved therapies. (Testing for genomic
alterations besides EGFR, ALK, and ROS1 is not required prior to
randomization). Subjects with squamous NSCLC are only required to undergo EGFR,
ALK, and ROS1 testing if they have no history of tobacco smoking or were
diagnosed with NSCLC at <40 years of age. Subjects whose tumors harbor KRAS
mutations are eligible for the study.
4. Has provided a formalin-fixed tumor tissue sample (minimum of 4 × 4-micron
sections or block equivalent) for the measurement of TROP2 protein expression
and for the assessment of other exploratory biomarkers. This tissue requirement
is in addition to the tissue required for PD-L1 testing for tissue screening
purposes. If a documented law or regulation prohibits (or does not approve)
sample collection, then such sample will not be collected.
5. Tumor has high PD-L1 expression (TPS >=50%) as determined by PDL1 IHC 22C3
pharmDx assay by central testing (minimum of 6 slides).
6. Has an adequate treatment washout period before Cycle 1 Day 1 as defined in
protocol Section 5.1.
7. Measurable disease based on local imaging assessment using RECIST Version
1.1 (see Section 10.4 of the protocol).
8. Has left ventricular ejection fraction (LVEF) >=50% by either an
echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 28 days
before randomization.
9. ECOG PS of 0 or 1 at screening.
10. Has a life expectancy of at least 3 months.
11. Adequate bone marrow function within 7 days before randomization as defined
in protocol Section 5.1.
12. If the subject is a female of childbearing potential, she must not be
pregnant, breastfeeding or intend to become pregnant during the study; she must
also have a negative serum pregnancy test at screening and must be willing to
use highly effective birth control (as detailed in protocol Section 10.3.4) or
avoid heterosexual intercourse upon randomization, during the Treatment Period,
for 7 months following the last dose of Dato-DXd, and for 4 months following
the last dose of pembrolizumab, whichever occurs later. A female is considered
of childbearing potential following menarche and until becoming postmeno
1. Has received prior systemic treatment for advanced or metastatic NSCLC.
2. Has received prior treatment for NSCLC with any of the following, including
in the adjuvant/neoadjuvant setting:
a. Any agent, including an antibody-drug conjugate, containing a
chemotherapeutic agent targeting topoisomerase I.
b. TROP2-targeted therapy.
c. Any anti-programmed death receptor-1 (PD-1), anti-PD-L1, or anti- PD-ligand
2 (L2) agent or with an agent directed to another stimulatory or co-inhibitory
T-cell receptor (eg, CTLA-4, OX40, CD137).
d. Any other immune checkpoint inhibitors. Subjects who received adjuvant or
neoadjuvant therapy OTHER than those listed above, are eligible if the
adjuvant/neoadjuvant therapy was completed at least 6 months prior to the
diagnosis of advanced/metastatic disease.
3. Has spinal cord compression or active and untreated central nervous system
(CNS) metastases and/or carcinomatous meningitis. Subjects with previously
treated brain metastases may participate provided they are radiologically
stable (ie, without evidence of progression) for at least 2 weeks by repeat
imaging (note: repeat imaging should be performed during study screening),
clinically stable, and without requirement of steroid treatment for at least 7
days before the first dose of study drug.
Note: A computed tomography (CT) scan or magnetic resonance imaging (MRI) scan
of the brain at baseline (MRI preferred) is required for all subjects. For
those subjects in whom 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 4 weeks later (in
which case, repeat of all screening activity may be required).
4. Has received prior radiotherapy <=4 weeks of start of study intervention or
more than 30Gy to the lung within 6 months of Cycle 1 Day 1. Subjects must have
recovered from all radiation related toxicities, without requiring
corticosteroids. A 2- week washout is permitted for palliative radiation to the
non-thoracic region.
5. History of another primary malignancy (beyond NSCLC) except for the
following:
- Malignancy treated with curative intent and with no known active disease >=3
years before the first dose of study treatment and of low potential risk for
recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- Participants with a history of prostate cancer (tumor/node/metastasis stage)
of Stage <=T2cN0M0 without biochemical recurrence or progression and who in the
opinion of the investigator are not deemed to require active intervention.
6. Has a history of (non-infectious) interstitial lung disease
(ILD)/pneumonitisn including radiations pneumonitis that required steroids, has
current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled
out by imaging at screening.
7. Clinically severe pulmonary compromise, as judged by the investigator,
resulting from intercurrent pulmonary illnesses including, but not limited to,
any underlying pulmonary disorder (eg, pulmonary emboli diagnosed within 3
months of Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary
disease, restrictive lung disease, pleural
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method