Datopotamab Deruxtecan / Rilvegostomig / Pembrolizumab · Phase 3 Trial

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

ClinicalTrials.gov · August 12, 2026

Preliminary Why this matters to you Expert discussion

Early or partial results. Treat as a signal, not a conclusion.

AI Summary

This is a planned Phase 3, open-label study comparing Dato-DXd plus rilvegostomig or rilvegostomig monotherapy against pembrolizumab monotherapy in first-line advanced non-squamous NSCLC with high PD-L1 expression. No results are reported in this registry record; the study is currently recruiting.

What was studied

Phase 3, Interventional, Randomized, Parallel, Single masking, Treatment purpose. Non-Small Cell Lung Cancer; age from 18 Years. Intervention: Arm 1: Datopotamab Deruxtecan in Combination With Rilvegost…; Arm 2: Rilvegostomig Monotherapy. Compared with: Arm 3: Pembrolizumab Monotherapy — Active Comparator. n = 675. 287 sites across 21 countries.

Key findings

Safety

Registry record only; no efficacy or safety results reported.

Who this may help

Once results are available, this trial will directly assess whether combining a TROP2-directed antibody–drug conjugate (Dato-DXd) with a TGF-β inhibitor (rilvegostomig) improves outcomes over standard checkpoint inhibition in a defined NSCLC population. Clinicians should await published primary analysis.

Plain-language summary

This is a clinical trial registry record describing a planned Phase 3 study with no results posted; it documents design and enrollment targets only.

Study design

As stated by the source record.

MethodsPrimary outcome measures: Progression-Free Survival (PFS) in TROP2 biomarker positive participants. (assessed at Approximately 4 years); Overall Survival (OS) in TROP2 biomarker positive participants. (assessed at Approximately 6 years)

DesignPhase 3, Interventional, Randomized, Parallel, Single masking, Treatment purpose

PopulationNon-Small Cell Lung Cancer; age from 18 Years

Sample size675

InterventionArm 1: Datopotamab Deruxtecan in Combination With Rilvegost…; Arm 2: Rilvegostomig Monotherapy

ComparatorArm 3: Pembrolizumab Monotherapy — Active Comparator

Setting287 sites across 21 countries

Reported figures

Quoted from the source exactly as published.

Planned enrollment675

PhasePHASE3

Primary outcome measure 1Progression-Free Survival (PFS) in TROP2 biomarker positive participants, Approximately 4 years follow-up

Primary outcome measure 2Overall Survival (OS) in TROP2 biomarker positive participants, Approximately 6 years follow-up

Clinical bottom line

Caveats

Registry record only; no efficacy or safety results reported.
Open-label design; no blinding of participants or investigators.
Recruitment status currently active; final enrollment and completion status unknown.
Comparator is pembrolizumab monotherapy (standard of care in this population as of registration); no active chemotherapy arm described.

Evidence assessment

Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.

Study design

moderate

Phase 3, open-label, three-arm interventional design appropriate for efficacy assessment.

Directness

strong

Hard clinical endpoints (PFS, OS) in relevant population: advanced NSCLC, high PD-L1.

Consistency

insufficient

No results reported; cannot assess consistency with other evidence.

Risk of bias

limited

Open-label design introduces bias risk; no blinding described.

Sample adequacy

moderate

Estimated enrollment 675 participants; adequate for Phase 3 but enrollment not yet complete.

What is missing. This record has no key findings. That is a gap in the analysis, not a judgement about the study.

Source abstract

Registry record from ClinicalTrials.gov (NCT06357533). This is a study registration, not published results. Lead sponsor: AstraZeneca. Recruitment status: RECRUITING. Phase: PHASE3. Study type: INTERVENTIONAL. Enrollment: 675 participants (ESTIMATED). Conditions: Non-Small Cell Lung Cancer. Interventions: DRUG: Datopotamab Deruxtecan; DRUG: Rilvegostomig; DRUG: Pembrolizumab. Primary outcome measures: Progression-Free Survival (PFS) in TROP2 biomarker positive participants. , Approximately 4 years; Overall Survival (OS) in TROP2 biomarker positive participants. , Approximately 6 years. 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.

Follow from this

Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.

Datopotamab DeruxtecanRilvegostomigNCT06357533PembrolizumabAstraZenecaNon Small Cell Lung Cancer