Recruiting
Phase 3

Dato-DXd & Rilvegostomig

Sponsor:

AstraZeneca

Code:

NCT06357533

Conditions

Non-Small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Datopotamab Deruxtecan

Rilvegostomig

Pembrolizumab

Study Details

Brief summary:

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.

Conditions

Non-Small Cell Lung Cancer

Study ID

NCT06357533

Start date

Apr 11, 2024

Status verified date

Aug, 2026

Completion date

Dec 28, 2029

Anticipated

Primary completion date

Dec 28, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Enrollment

675 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

Interventions

Datopotamab Deruxtecan

Datopotamab Deruxtecan IV (intravenous)

Rilvegostomig

Rilvegostomig IV (intravenous)

Pembrolizumab

Pembrolizumab IV (intravenous)

Primary outcome measure

  • Progression-Free Survival (PFS) in TROP2 biomarker positive participants. [ Time Frame: Approximately 4 years ]
  • Overall Survival (OS) in TROP2 biomarker positive participants. [ Time Frame: Approximately 6 years ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

Locations

Research Site

Recruiting

Anchorage, Alaska, United States, 99508

Research Site

Recruiting

Tucson, Arizona, United States, 85719

Research Site

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Little Rock, Arkansas, United States, 72205

Research Site

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Springdale, Arkansas, United States, 72762

Research Site

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Anaheim, California, United States, 92801

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Beverly Hills, California, United States, 90211

Research Site

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Fountain Valley, California, United States, 92708

Research Site

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Clermont, Florida, United States, 34711

Research Site

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Gainesville, Florida, United States, 32608

Research Site

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Miami Beach, Florida, United States, 33140

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Orange City, Florida, United States, 32763

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Orlando, Florida, United States, 32806

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West Palm Beach, Florida, United States, 33401

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Atlanta, Georgia, United States, 30318

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Atlanta, Georgia, United States, 30322

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Hinsdale, Illinois, United States, 60521

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Noblesville, Indiana, United States, 46062

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Paducah, Kentucky, United States, 42003

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Annapolis, Maryland, United States, 21401

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Boston, Massachusetts, United States, 02114

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Boston, Massachusetts, United States, 02215

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Dearborn, Michigan, United States, 48126

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Farmington Hills, Michigan, United States, 48334

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Grand Rapids, Michigan, United States, 49503

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Hattiesburg, Mississippi, United States, 39401

Research Site

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Kansas City, Missouri, United States, 64132

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Grand Island, Nebraska, United States, 68803

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Omaha, Nebraska, United States, 68130

Research Site

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Las Vegas, Nevada, United States, 89102

Research Site

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Stony Brook, New York, United States, 11794

Research Site

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Greenville, North Carolina, United States, 27834

Research Site

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Salisbury, North Carolina, United States, 28144

Research Site

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Cincinnati, Ohio, United States, 45219

Research Site

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Maumee, Ohio, United States, 43537

Research Site

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Toledo, Ohio, United States, 43623

Research Site

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Greenville, South Carolina, United States, 29607

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Sioux Falls, South Dakota, United States, 57105

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Fort Worth, Texas, United States, 76104

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Houston, Texas, United States, 77030

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Kingwood, Texas, United States, 77339

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Odessa, Texas, United States, 79761

Research Site

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Fort Belvoir, Virginia, United States, 22060

Research Site

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Leesburg, Virginia, United States, 20176

Research Site

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Midlothian, Virginia, United States, 23114

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Richmond, Virginia, United States, 23230

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Tacoma, Washington, United States, 98405

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Vancouver, Washington, United States, 98684

Research Site

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Wenatchee, Washington, United States, 98801

Research Site

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Appleton, Wisconsin, United States, 54911

Research Site

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Vancouver, British Columbia, Canada, VSZ 4E6

Research Site

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St. John's, Newfoundland and Labrador, Canada, A1B 3V6

Research Site

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London, Ontario, Canada, N6A 4L6

Research Site

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Oshawa, Ontario, Canada, L1G 2B9

Research Site

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Lévis, Quebec, Canada, G6V 0B8

Research Site

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Montreal, Quebec, Canada, H3T 1E2

Research Site

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Montreal, Quebec, Canada, H3T 1M5

Research Site

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Montreal, Quebec, Canada, H4J 1C5

Research Site

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Rimouski, Quebec, Canada, G5L 5T1

Research Site

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Trois-Rivières, Quebec, Canada, G8Z 3R9

Research Site

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Saskatoon, Saskatchewan, Canada, S7N 4H4

Research Site

Recruiting

Chicoutimi, Canada, G7H 5H6

More Information

Sponsor

AstraZeneca

Last update posted

Aug 12, 2026

Last verified

Aug, 2026

Keywords

  • NSCLC
  • Non-Small Cell Lung Cancer
  • Datopotamab Deruxtecan
  • Rilvegostomig
  • Pembrolizumab
  • Non-squamous
  • PD-L1 expression >=50%
  • Locally-advanced NSCLC
  • Metastatic NSCLC

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-08-12.