Phase III, Open-label, Study of First-line Dato-DXd in Combination With Rilvegostomig for Advanced Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations
Purpose
The purpose of this study is to evaluate efficacy and safety of Dato-DXd in combination with rilvegostomig or rilvegostomig monotherapy compared with pembrolizumab monotherapy as a first line therapy in participants with locally advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.
Condition
- Non-Small Cell Lung Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Histologically or cytologically documented non-squamous NSCLC. - Stage IIIB or IIIC or Stage IV metastatic NSCLC (according to Edition 8 of the AJCC staging manual) not amenable to curative surgery or definitive chemoradiation. - Absence of sensitising EGFR mutations, and ALK and ROS1 rearrangements, and absence of documented local test result for any other known genomic alteration for which there are locally approved and available targeted first-line therapies. - Must provide tumor sample to determine PD-L1 status, TROP2 status and other biomarkers. - Known tumour PD-L1 expression status defined as TC ≥ 50% - At least one lesion, not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline - ECOG performance status of 0 or 1 - Adequate bone marrow reserve and organ function
Exclusion Criteria
- Prior systemic therapy for advanced/metastatic NSCLC. - Squamous cell histology, or predominantly squamous cell histology NSCLC; mixed small cell lung cancer; NSCLC histology, sarcomatoid variant. - History of another primary malignancy within 3 years - Active or prior documented autoimmune or inflammatory disorders (with exceptions) - Any evidence of severe or uncontrolled disease that makes it undesirable for the participant to participate in the study or that would jeopardies compliance with the protocol. - Has clinically significant third-space fluid retention (for example pleural effusion) and is not amenable for repeated drainage. - History of any ILD/pneumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, has current or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. - Has significant pulmonary function compromise, as determined by the investigator - Spinal cord compression, or brain metastases unless participant treated and no longer symptomatic, radiologically stable, and who require no treatment with corticosteroids or anticonvulsants. - History of leptomeningeal carcinomatosis - Known clinically significant corneal disease - Active infection with TB, HBV, HCV, Hepatitis A, or known HIV infection that is not well controlled - History of active primary immunodeficiency
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
- Masking Description
- Open-label, sponsor-blinded
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm 1: Datopotamab Deruxtecan in Combination With Rilvegostomig |
Participants in the Datopotamab Deruxtecan (Dato-DXd) in combination with Rilvegostomig group will receive Dato-DXd plus rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle. |
|
|
Experimental Arm 2: Rilvegostomig Monotherapy |
Participants in the rilvegostomig monotherapy group will receive rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle. |
|
|
Active Comparator Arm 3: Pembrolizumab Monotherapy |
Participants in the pembrolizumab group will receive pembrolizumab as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle. |
|
Recruiting Locations
Research Site
Anchorage, Alaska 99508
Anchorage, Alaska 99508
Research Site
Tucson, Arizona 85719
Tucson, Arizona 85719
Research Site
Little Rock, Arkansas 72205
Little Rock, Arkansas 72205
Research Site
Springdale, Arkansas 72762
Springdale, Arkansas 72762
Research Site
Anaheim, California 92801
Anaheim, California 92801
Research Site
Beverly Hills, California 90211
Beverly Hills, California 90211
Research Site
Fountain Valley, California 92708
Fountain Valley, California 92708
Research Site
Clermont, Florida 34711
Clermont, Florida 34711
Research Site
Gainesville, Florida 32608
Gainesville, Florida 32608
Research Site
Miami Beach, Florida 33140
Miami Beach, Florida 33140
Research Site
Orange City, Florida 32763
Orange City, Florida 32763
Research Site
Orlando, Florida 32806
Orlando, Florida 32806
Research Site
West Palm Beach, Florida 33401
West Palm Beach, Florida 33401
Research Site
Atlanta, Georgia 30318
Atlanta, Georgia 30318
Research Site
Atlanta, Georgia 30322
Atlanta, Georgia 30322
Research Site
Hinsdale, Illinois 60521
Hinsdale, Illinois 60521
Research Site
Noblesville, Indiana 46062
Noblesville, Indiana 46062
Research Site
Paducah, Kentucky 42003
Paducah, Kentucky 42003
Research Site
Annapolis, Maryland 21401
Annapolis, Maryland 21401
Research Site
Boston, Massachusetts 02114
Boston, Massachusetts 02114
Research Site
Boston, Massachusetts 02215
Boston, Massachusetts 02215
Research Site
Dearborn, Michigan 48126
Dearborn, Michigan 48126
Research Site
Farmington Hills, Michigan 48334
Farmington Hills, Michigan 48334
Research Site
Grand Rapids, Michigan 49503
Grand Rapids, Michigan 49503
Research Site
Hattiesburg, Mississippi 39401
Hattiesburg, Mississippi 39401
Research Site
Kansas City, Missouri 64132
Kansas City, Missouri 64132
Research Site
Grand Island, Nebraska 68803
Grand Island, Nebraska 68803
Research Site
Omaha, Nebraska 68130
Omaha, Nebraska 68130
Research Site
Las Vegas, Nevada 89102
Las Vegas, Nevada 89102
Research Site
Stony Brook, New York 11794
Stony Brook, New York 11794
Research Site
Greenville, North Carolina 27834
Greenville, North Carolina 27834
Research Site
Salisbury, North Carolina 28144
Salisbury, North Carolina 28144
Research Site
Cincinnati, Ohio 45219
Cincinnati, Ohio 45219
Research Site
Maumee, Ohio 43537
Maumee, Ohio 43537
Research Site
Toledo, Ohio 43623
Toledo, Ohio 43623
Research Site
Greenville, South Carolina 29607
Greenville, South Carolina 29607
Research Site
Sioux Falls, South Dakota 57105
Sioux Falls, South Dakota 57105
Research Site
Fort Worth, Texas 76104
Fort Worth, Texas 76104
Research Site
Houston, Texas 77030
Houston, Texas 77030
Research Site
Kingwood, Texas 77339
Kingwood, Texas 77339
Research Site
Odessa, Texas 79761
Odessa, Texas 79761
Research Site
Fort Belvoir, Virginia 22060
Fort Belvoir, Virginia 22060
Research Site
Leesburg, Virginia 20176
Leesburg, Virginia 20176
Research Site
Midlothian, Virginia 23114
Midlothian, Virginia 23114
Research Site
Richmond, Virginia 23230
Richmond, Virginia 23230
Research Site
Tacoma, Washington 98405
Tacoma, Washington 98405
Research Site
Vancouver, Washington 98684
Vancouver, Washington 98684
Research Site
Wenatchee, Washington 98801
Wenatchee, Washington 98801
Research Site
Appleton, Wisconsin 54911
Appleton, Wisconsin 54911
Research Site
San Juan, Puerto Rico 00909
San Juan, Puerto Rico 00909
More Details
- Status
- Recruiting
- Sponsor
- AstraZeneca
Study Contact
AstraZeneca Clinical Study Information Center1-877-240-9479
information.center@astrazeneca.com
Detailed Description
This is a Phase III, randomized, open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig monotherapy compared with Pembrolizumab monotherapy for the first-line treatment of participants with locally-advanced or metastatic non-squamous NSCLC with high PD-L1 expression (TC ≥ 50%) and without actionable genomic alterations.