RECRUITING

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

Conditions

Metastatic Non Small Cell Lung Cancer Advanced Non Small Cell Lung Cancer Datopotamab Deruxtecan (Dato-DXd)Pembrolizumab

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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)

Quick Facts

Study Start:2022-03-04

Study Completion:2028-04-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05215340

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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): 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). Participants with early-stage NSCLC who have relapsed should be restaged during screening to ensure their eligibility for the study. 2. 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. 3. 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.	* 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: 1. Any agent, including an antibody-drug conjugate, containing a chemotherapeutic agent targeting topoisomerase I. 2. TROP2-targeted therapy. 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 (eg, CTLA-4, OX40, CD137). 4. 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: 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. 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. 3. Adequately treated carcinoma in situ without evidence of disease. 4. 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. * Uncontrolled or significant cardiovascular disease, including: 1. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval \>470 ms regardless of sex (based on the average of the 12-lead electrocardiogram determination at screening). 2. Myocardial infarction within 6 months prior to randomization. 3. Uncontrolled angina pectoris within 6 months prior to randomization. 4. LVEF \<50% by ECHO or MUGA scan within 28 days before randomization. 5. New York Heart Association Class 2 to 4 congestive heart failure (CHF) at screening. 6. Uncontrolled hypertension (resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg) within 28 days before randomization. * Clinically significant corneal disease. * Has received a live vaccine or live-attenuated vaccine (messenger ribonucleic acid and replication-incompetent adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of study drug. For any participant receiving an approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine, please follow the vaccine label and/or local guidance. * Active, known, or suspected autoimmune disease (has an active autoimmune disease that has required systemic treatment in the past 2 years). * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosage \>10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy ≤7 days prior to the first dose of study drug. * Has known human immunodeficiency virus (HIV) infection that is not well controlled. * Has an active hepatitis or uncontrolled hepatitis B or active hepatitis C infection. * Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. * Had an allogeneic tissue/solid organ transplant. * Has a history of severe hypersensitivity reactions to either the drug or inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd or pembrolizumab.

Inclusion Criteria

Exclusion Criteria

* 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):
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). Participants with early-stage NSCLC who have relapsed should be restaged during screening to ensure their eligibility for the study.
2. 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.
3. 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.

* 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:
1. Any agent, including an antibody-drug conjugate, containing a chemotherapeutic agent targeting topoisomerase I.
2. TROP2-targeted therapy.
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 (eg, CTLA-4, OX40, CD137).
4. 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:
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.
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
3. Adequately treated carcinoma in situ without evidence of disease.
4. 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.
* Uncontrolled or significant cardiovascular disease, including:
1. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval \>470 ms regardless of sex (based on the average of the 12-lead electrocardiogram determination at screening).
2. Myocardial infarction within 6 months prior to randomization.
3. Uncontrolled angina pectoris within 6 months prior to randomization.
4. LVEF \<50% by ECHO or MUGA scan within 28 days before randomization.
5. New York Heart Association Class 2 to 4 congestive heart failure (CHF) at screening.
6. Uncontrolled hypertension (resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg) within 28 days before randomization.
* Clinically significant corneal disease.
* Has received a live vaccine or live-attenuated vaccine (messenger ribonucleic acid and replication-incompetent adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of study drug. For any participant receiving an approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine, please follow the vaccine label and/or local guidance.
* Active, known, or suspected autoimmune disease (has an active autoimmune disease that has required systemic treatment in the past 2 years).
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosage \>10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy ≤7 days prior to the first dose of study drug.
* Has known human immunodeficiency virus (HIV) infection that is not well controlled.
* Has an active hepatitis or uncontrolled hepatitis B or active hepatitis C infection.
* Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
* Had an allogeneic tissue/solid organ transplant.
* Has a history of severe hypersensitivity reactions to either the drug or inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd or pembrolizumab.

Contacts and Locations

Study Contact

(US Sites) Daiichi Sankyo Contact for Clinical Trial Information

CONTACT

908-992-6400

CTRinfo@dsi.com

(Asia Sites) Daiichi Sankyo Contact for Clinical Trial Informat

CONTACT

+81-3-6225-1111(M-F 9-5 JST)

dsclinicaltrial@daiichisankyo.co.jp

Principal Investigator

Global Clinical Leader

STUDY_DIRECTOR

Daiichi Sankyo

Study Locations (Sites)

Ironwood Cancer and Research Center

Chandler, Arizona, 85224

United States

UCLA HemOnc - Clinical Research Unit

Los Angeles, California, 90095

United States

Compassionate Cancer Care Medical Group

Riverside, California, 92501

United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158

United States

Ridley-Tree Cancer Center

Santa Barbara, California, 93105

United States

PIH Health Whittier Hospital

Whittier, California, 90602

United States

The Oncology Institute of Hope and Innovation

Whittier, California, 90603

United States

Uch-Mhs D/B/A Memorial Health System

Colorado Springs, Colorado, 80909

United States

Johns Hopkins University

Baltimore, Maryland, 21205

United States

American Oncology Partners of Maryland

Bethesda, Maryland, 20817

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

United States

DFCI - Steward St. Elizabeth's Medical Center

Boston, Massachusetts, 02215

United States

Dana Farber Cancer Institute - Foxborough

Foxboro, Massachusetts, 02035

United States

Dana Farber Cancer Institute - Milford Medical Center

Milford, Massachusetts, 01757

United States

DFCI - South Shore Hospital

South Weymouth, Massachusetts, 02190

United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03766

United States

Astera Cancer Care

East Brunswick, New Jersey, 08816

United States

Regional Cancer Care Associates LLC

Freehold, New Jersey, 07728

United States

Cooperman Barnabas Medical Center

New Brunswick, New Jersey, 08901

United States

The Valley Hospital

Paramus, New Jersey, 07652

United States

Montefiore Medical Center

Bronx, New York, 10461

United States

Arizona Oncology NAHOA

Irving, Texas, 75063

United States

Cancer Care Center of Brevard

Irving, Texas, 75063

United States

Illinois Cancer Specialists

Irving, Texas, 75063

United States

Maryland Oncology Hematology

Irving, Texas, 75063

United States

Southern Cancer Center

Irving, Texas, 75063

United States

Texas Oncology - Northeast Texas

Irving, Texas, 75063

United States

Texas Oncology Gulf Coast

Irving, Texas, 75063

United States

Texas Oncology McAllen

Irving, Texas, 75063

United States

Woodlands Medical

Irving, Texas, 75063

United States

University of Texas Health Science Center San Antonio

San Antonio, Texas, 78229

United States

Utah Cancer Specialists

Salt Lake City, Utah, 84106

United States

Providence Regional Cancer System

Lacey, Washington, 98503

United States

VA Puget Sound Health Care System - VAPSHCS

Seattle, Washington, 98108

United States

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Daiichi Sankyo

Global Clinical Leader, STUDY_DIRECTOR, Daiichi Sankyo

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-03-04

Study Completion Date2028-04-30

Study Record Updates

Study Start Date2022-03-04

Study Completion Date2028-04-30

Terms related to this study

Keywords Provided by Researchers

Metastatic Non Small Cell Lung Cancer
Advanced Non Small Cell Lung Cancer
Datopotamab Deruxtecan (Dato-DXd)
Pembrolizumab

Additional Relevant MeSH Terms

Metastatic Non Small Cell Lung Cancer