NCT05215340|RecruitingPhase 3DMCFDA Drug

Study of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects With Advanced or Metastatic NSCLC Without Actionable Genomic Alterations

TROPION-Lung08

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)

Daiichi Sankyo ClinicalTrials.gov

Compare

5 other identifiers

DS1062-A-U3042021-002555-10KEYNOTE-C73MK3475-C732023-507933-12-00

Study Type

interventional

Target

740

Locations

27 countries

Sites

241

Timeline

RegisteredJan 2022

StartedMar 2022

CompletionApr 2028

Brief Summary

This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab alone in participants with advanced or metastatic non-small cell lung cancer (NSCLC) of non-squamous histology.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

740

participants targeted

Target at P75+ for phase_3

Timeline

24mo left

Started Mar 2022

Longer than P75 for phase_3

Geographic Reach

27 countries

241 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.2 years study duration

Study Progress68%

Mar 2022Apr 2028

First Submitted

Initial submission to the registry

January 18, 2022

Completed

13 days until next milestone

First Posted

Study publicly available on registry

January 31, 2022

Completed

1 month until next milestone

Study Start

First participant enrolled

March 4, 2022

Completed

6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 29, 2028

Expected

2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2028

Last Updated

January 7, 2026

Status Verified

January 1, 2026

Enrollment Period

6 years

First QC Date

January 18, 2022

Last Update Submit

January 5, 2026

Conditions

Metastatic Non Small Cell Lung Cancer

Keywords

Metastatic Non Small Cell Lung CancerAdvanced Non Small Cell Lung CancerDatopotamab Deruxtecan (Dato-DXd)Pembrolizumab

Outcome Measures

Primary Outcomes (2)

Progression-free Survival Based on Blinded Independent Central Review in Participants With Non-Squamous Histology Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab
Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.
From randomization until disease progression or death (whichever occurs first), up to approximately 44 months
Overall Survival (OS) in Participants With Non-Squamous Histology Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab
Overall Survival (OS) is defined as the time from randomization to death due to any cause.
From randomization until date of death due to any cause, up to approximately 71 months

Secondary Outcomes (11)

OS in All Randomized Participants, Including Participants With Squamous and Non-Squamous Histology
From randomization until date of death due to any cause, up to approximately 71 months
PFS Based on BICR in All Randomized Participants, Including Participants With Squamous and Non-Squamous Histology
From randomization until disease progression or death (whichever occurs first), up to approximately 44 months
Progression-free Survival by Investigator in Participants with Non-Squamous Histology, and Separately for All Randomized Participants
From randomization until disease progression or death (whichever occurs first), up to approximately 44 months
Progression-free Survival 2 in Participants with Non-Squamous Histology, and Separately for All Randomized Participants
From randomization until disease progression on the next line of therapy or death (whichever occurs first), up to approximately 71 months
ORR by BICR and Investigator in Participants with Non-Squamous Histology, and Separately for All Randomized Participants
From randomization to first confirmed response, up to approximately 44 months
+6 more secondary outcomes

Study Arms (2)

Pembrolizumab + Datopotamab Deruxtecan (Dato-DXd)

EXPERIMENTAL

Participants will be randomized to receive 200 mg pembrolizumab followed by 6.0mg/kg Dato-DXd.

Drug: Datopotamab DeruxtecanDrug: Pembrolizumab

Pembrolizumb

ACTIVE COMPARATOR

Participants will be randomized to receive 200 mg pembrolizumab.

Drug: Pembrolizumab

Interventions

Datopotamab DeruxtecanDRUG

Dato-DXd will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.

Also known as: Dato-DXd

Pembrolizumab + Datopotamab Deruxtecan (Dato-DXd)

PembrolizumabDRUG

Pembrolizumab will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.

Also known as: KEYTRUDA®

Pembrolizumab + Datopotamab Deruxtecan (Dato-DXd)Pembrolizumb

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Sign and date the Tissue Screening and Main Informed Consent Forms, prior to the start of any study-specific qualification procedures.
Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time of informed consent.
Histologically documented non-squamous NSCLC that meets all of the following criteria (Note: Subjects with squamous histology were eligible prior to Protocol Version 5.0. After Protocol Version 5.0, subjects with squamous histology are not eligible. Subjects with mixed histology, including those with a squamous component, remain eligible the study even after Protocol Version 5.0):
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). Participants with early-stage NSCLC who have relapsed should be restaged during screening to ensure their eligibility for the study.
Documented negative test results for epidermal growth factor receptor (EGFR), lymphoma kinase (ALK), and proto-oncogene1 (ROS1) actionable genomic alterations (AGAs) 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.
No known AGAs in neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), rearranged during transfection (RET), mesenchymal-epithelial transition factor (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 whose tumors harbor KRAS mutations are eligible for the study.
Has provided a formalin-fixed tumor tissue sample for the measurement of trophoblast cell surface protein 2 (TROP2) protein expression and for the assessment of other exploratory biomarkers.
Tumor has high programmed death receptor-1 (PD-L1) expression (TPS ≥50%) as determined by PD-L1 immunohistochemistry (IHC) 22C3 pharmDx assay by central testing (minimum of 6 slides).
Has an adequate treatment washout period before Cycle 1 Day 1.
Measurable disease based on local imaging assessment using RECIST Version 1.1.
Has left ventricular ejection fraction (LVEF) ≥50% by either an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 28 days before randomization.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at screening.
Has a life expectancy of at least 3 months.
Adequate bone marrow function within 7 days before randomization.

You may not qualify if:

Has received prior systemic treatment for advanced or metastatic NSCLC.
Has received prior treatment for NSCLC with any of the following, including in the adjuvant/neoadjuvant setting:
Any agent, including an antibody-drug conjugate, containing a chemotherapeutic agent targeting topoisomerase I.
TROP2-targeted therapy.
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).
Any other immune checkpoint inhibitors. Participants 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.
Has spinal cord compression or active and untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases and who are asymptomatic may participate provided they are radiologically stable.
Has received prior radiotherapy \< 4 weeks of start of study intervention or more than 30 Gy (unit of ionizing radiation dose in the International System of Units) to the lung within 6 months of Cycle 1 Day 1.
History of another primary malignancy (beyond NSCLC) except for:
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.
Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
Clinically severe pulmonary compromise, as judged by the investigator, resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement or prior complete pneumonectomy.
+17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (243)

Ironwood Cancer and Research Center

Chandler, Arizona, 85224, United States

RECRUITING

UCLA HemOnc - Clinical Research Unit

Los Angeles, California, 90095, United States

RECRUITING

Compassionate Cancer Care Medical Group

Riverside, California, 92501, United States

WITHDRAWN

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

WITHDRAWN

Ridley-Tree Cancer Center

Santa Barbara, California, 93105, United States

RECRUITING

PIH Health Whittier Hospital

Whittier, California, 90602, United States

RECRUITING

The Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

TERMINATED

Uch-Mhs D/B/A Memorial Health System

Colorado Springs, Colorado, 80909, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21205, United States

RECRUITING

American Oncology Partners of Maryland

Bethesda, Maryland, 20817, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

DFCI - Steward St. Elizabeth's Medical Center

Boston, Massachusetts, 02215, United States

WITHDRAWN

Dana Farber Cancer Institute - Foxborough

Foxborough, Massachusetts, 02035, United States

TERMINATED

Dana Farber Cancer Institute - Milford Medical Center

Milford, Massachusetts, 01757, United States

WITHDRAWN

DFCI - South Shore Hospital

South Weymouth, Massachusetts, 02190, United States

TERMINATED

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

RECRUITING

Astera Cancer Care

East Brunswick, New Jersey, 08816, United States

RECRUITING

Regional Cancer Care Associates LLC

Freehold, New Jersey, 07728, United States

RECRUITING

Cooperman Barnabas Medical Center

New Brunswick, New Jersey, 08901, United States

TERMINATED

The Valley Hospital

Paramus, New Jersey, 07652, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10461, United States

RECRUITING

Arizona Oncology NAHOA