A randomized, open-label, Phase III 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)

Syneos Health (Germany)0 sites740 target enrollmentMay 16, 2022

ConditionsCancer Advanced or metastatic non-small cell lung cancer (NSCLC)

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: Cancer
Sponsor: Syneos Health (Germany)
Enrollment: 740
Status: Active, not recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

May 16, 2022

End Date

May 31, 2025

Last Updated

3 years ago

Study Type

Interventional

Sex

All

Investigators

Sponsor

Syneos Health (Germany)

Eligibility Criteria

Inclusion Criteria

•1\. Sign and date the Tissue Screening and Main ICFs, prior to the start of any study\-specific qualification procedures
•2\. Adults aged \=18 years or the minimum legal adult age (whichever is greater) at the time of informed consent (following 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:
•3\.1\. 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)
•3\.2\. 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
•3\.3\. 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 enrollment)
•4\. Has provided a formalin\-fixed tumor tissue sample (minimum of 10 \[preferably 15] × 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 PD\-L1 IHC 22C3 pharmDx assay by central testing (minimum of six 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

Exclusion Criteria

•1\. Has received prior systemic treatment for advanced or metastatic NSCLC
•2\. Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting:
•2\.1\. Any agent, including an antibody\-drug conjugate, containing a chemotherapeutic agent targeting topoisomerase I
•2\.2\. TROP2\-targeted therapy
•2\.3\. 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 (e.g., CTLA\-4, OX40, CD137\)
•2\.4\. 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 4 weeks by repeat imaging (note: repeat imaging should be performed during study screening), clinically stable, and without the 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 a delay of study treatment to document the stability of CNS metastases with repeat imaging at least 4 weeks later (in which case, a repeat of all screening activity may be required).
•4\. Has received prior radiotherapy \=4 weeks of the start of the study intervention or more than 30 Gy to the lung within 6 months of Cycle 1 Day 1\. Subjects must have recovered from all radiation\-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 2\-week washout is permitted for palliative radiation (\=2 weeks of radiotherapy) to non\-CNS disease.
•5\. History of another primary malignancy (beyond NSCLC) except for:
•5\.1\. 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