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OncoMatch/Clinical Trials/NCT05215340

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

Is NCT05215340 recruiting? Yes, currently enrolling (May 2026). This Phase 3 trial studies multiple treatments including Datopotamab Deruxtecan and Pembrolizumab for metastatic non small cell lung cancer.

Phase 3RecruitingDaiichi SankyoNCT05215340Data as of May 2026

Treatment: Datopotamab Deruxtecan · PembrolizumabThis 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.

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Extracted eligibility criteria

Cancer type

Small Cell Lung Cancer

Biomarker criteria

Required: EGFR wild-type

Documented negative test results for epidermal growth factor receptor (EGFR)...actionable genomic alterations (AGAs)

Required: ALK wild-type

Documented negative test results for...lymphoma kinase (ALK)...actionable genomic alterations (AGAs)

Required: ROS1 wild-type

Documented negative test results for...proto-oncogene1 (ROS1) actionable genomic alterations (AGAs)

Required: NTRK1 wild-type

No known AGAs in neurotrophic tyrosine receptor kinase (NTRK)...

Required: NTRK2 wild-type

No known AGAs in neurotrophic tyrosine receptor kinase (NTRK)...

Required: NTRK3 wild-type

No known AGAs in neurotrophic tyrosine receptor kinase (NTRK)...

Required: BRAF wild-type

No known AGAs in...proto-oncogene B-raf (BRAF)...

Required: RET wild-type

No known AGAs in...rearranged during transfection (RET)...

Required: MET wild-type

No known AGAs in...mesenchymal-epithelial transition factor (MET)...

Required: PD-L1 (CD274) high expression (TPS ≥50%) (TPS ≥50%)

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

Disease stage

Required: Stage IIIB, IIIC, IV

Performance status

ECOG 0–1(Restricted strenuous activity)

Prior therapy

No prior treatment (treatment-naive required)
Max 0 prior lines

Cannot have received: systemic treatment for advanced or metastatic NSCLC

Has received prior systemic treatment for advanced or metastatic NSCLC

Cannot have received: topoisomerase I inhibitor (including antibody-drug conjugate)

Any agent, including an antibody-drug conjugate, containing a chemotherapeutic agent targeting topoisomerase I

Cannot have received: TROP2-targeted therapy

TROP2-targeted therapy

Cannot have received: anti-PD-1 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)

Cannot have received: immune checkpoint inhibitor

Any other immune checkpoint inhibitors

Lab requirements

Blood counts

Adequate bone marrow function within 7 days before randomization

Cardiac function

LVEF ≥50% by ECHO or MUGA within 28 days before randomization; no NYHA Class 2-4 CHF; QTcF ≤470 ms; no recent MI or uncontrolled angina

Has left ventricular ejection fraction (LVEF) ≥50% by either an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 28 days before randomization. Adequate bone marrow function within 7 days before randomization. Uncontrolled or significant cardiovascular disease, including: 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). Myocardial infarction within 6 months prior to randomization. Uncontrolled angina pectoris within 6 months prior to randomization. LVEF <50% by ECHO or MUGA scan within 28 days before randomization. New York Heart Association Class 2 to 4 congestive heart failure (CHF) at screening. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) within 28 days before randomization.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Ironwood Cancer and Research Center · Chandler, Arizona
  • UCLA HemOnc - Clinical Research Unit · Los Angeles, California
  • Compassionate Cancer Care Medical Group · Riverside, California
  • UCSF Helen Diller Family Comprehensive Cancer Center · San Francisco, California
  • Ridley-Tree Cancer Center · Santa Barbara, California

Showing up to 5 US sites. See all sites on ClinicalTrials.gov →

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