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OncoMatch/Clinical Trials/NCT06899126

Study of Trastuzumab Deruxtecan, Pembrolizumab, and Platinum-based Chemotherapy in First-line HER2 Overexpressing Non-small Cell Lung Cancer

Is NCT06899126 recruiting? Yes, currently enrolling (May 2026). This Phase 3 trial studies multiple treatments including Trastuzumab Deruxtecan and pembrolizumab for non-small cell lung cancer.

Phase 3RecruitingDaiichi SankyoNCT06899126Data as of May 2026

Treatment: Trastuzumab Deruxtecan · pembrolizumab · Pemetrexed · ChemotherapyThis clinical trial is designed to assess the efficacy and safety of trastuzumab deruxtecan (T-DXd; Enhertu®) in combination with pembrolizumab versus platinum-based chemotherapy in combination with pembrolizumab in participants with no prior therapy for locally advanced unresectable or metastatic non-squamous NSCLC, whose tumors have HER2-overexpressing and PD-L1 TPS \<50% without known AGA that have locally available therapies targeting their AGAs in first-line advanced/metastatic setting.

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Extracted eligibility criteria

Cancer type

Non-Small Cell Lung Carcinoma

Biomarker criteria

Required: HER2 (ERBB2) overexpression

assessment of HER2 and PD-L1 expression by central or Sponsor-specified laboratory

Required: HER2 (ERBB2) mutation

Has no known HER2 mutation based on existing test results (if approved or validated local test is available)

Required: PD-L1 (CD274) expression

assessment of HER2 and PD-L1 expression by central or Sponsor-specified laboratory

Disease stage

Required: Stage IV, IIIB, IIIC

Prior therapy

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

Cannot have received: systemic anticancer therapy

Exception: adjuvant or neoadjuvant therapy (including ICI or platinum-based regimen) allowed if last dose ≥6 months before first trial dose and no progression on or within 6 months of last dose

Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC. Participants who received adjuvant or neoadjuvant therapy other than those listed below, including ICI (ie, anti-PD-1/PD-L1) or a platinum-based regimen, are eligible if the last dose of adjuvant/neoadjuvant therapy was given at least 6 months before the date of the first trial dose and should not have progressed on or within 6 months of the last dose date of adjuvant/neoadjuvant therapy.

Cannot have received: topoisomerase I inhibitor (including ADCs containing a chemotherapeutic agent targeting topoisomerase I)

Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I.

Cannot have received: HER2-targeted antibody-based anticancer therapy

HER2-targeted antibody-based anticancer therapy.

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

US trial sites

  • Alaska Oncology & Hematology, LLC · Anchorage, Alaska
  • Orange Coast Memorial Medical Center Fountain Valley · Fountain Valley, California
  • California Research Institute · Los Angeles, California
  • Los Angeles Cancer Network (LACN) · Los Angeles, California
  • Providence Medical Foundation · Santa Rosa, California

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

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