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OncoMatch/Clinical Trials/NCT04686305

Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC

Is NCT04686305 recruiting? Yes, currently enrolling (May 2026). This Phase 1 trial studies multiple treatments for locally advanced or metastatic non-small cell lung cancer.

Phase 1RecruitingAstraZenecaNCT04686305Data as of May 2026

Treatment: T-DXd · Durvalumab · Cisplatin · Carboplatin · Pemetrexed · Volrustomig · RilvegostomigDESTINY-Lung03 will investigate the safety and tolerability of trastuzumab deruxtecan in combination with Immunotherapy Agents with and without chemotherapy in patients with HER2 over-expressing non-small cell lung cancer. The efficacy will be also analyzed as a secondary endpoint.

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Extracted eligibility criteria

Cancer type

Non-Small Cell Lung Carcinoma

Biomarker criteria

Required: HER2 (ERBB2) overexpression

HER2 overexpression status as determined by central review of tumor tissue

Excluded: HER2 (ERBB2) mutation

HER2 mutation if previously known

Disease stage

Metastatic disease required

Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC

Performance status

WHO/ECOG 0–1

Prior therapy

Max 2 prior lines
Min 1 prior line

Must have received: systemic therapy — recurrent or metastatic

Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting

Cannot have received: anti-PD-1 therapy

Part 3, Part 4 and Part 5 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting

Cannot have received: anti-PD-L1 therapy

Part 3, Part 4 and Part 5 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting

Cannot have received: anti-CTLA-4 therapy

Part 3, Part 4 and Part 5 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting

Cannot have received: anti-TIGIT therapy

Part 3, Part 4 and Part 5 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting

Cannot have received: experimental immunotherapy

Part 3, Part 4 and Part 5 patients must not have had prior exposure to anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-TIGIT or any other experimental immunotherapy in any setting

Lab requirements

Blood counts

adequate organ and bone marrow function

Kidney function

Liver function

Cardiac function

No medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (NYHA Class II to IV), clinically important cardiac arrhythmias, or recent (< 6 months) cardiovascular event including stroke. For Part 3, Part 4 and Part 5: Cardiomyopathy of any etiology, symptomatic CHF (NYHA Class > II), unstable angina pectoris, history of MI within the past 12 months, or cardiac arrhythmia are to be excluded. Patients with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before treatment assignment to rule out acute cardiopulmonary events.

Has protocol defined adequate organ and bone marrow function. Medical history of myocardial infarction within 6 months before treatment assignment, symptomatic CHF (New York Heart Association Class II to IV), clinically important cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke. For Part 3, Part 4 and Part 5: Cardiomyopathy of any etiology, symptomatic CHF (as defined by New York Heart Association Class > II), unstable angina pectoris, history of MI within the past 12 months, or cardiac arrhythmia are to be excluded. Patients with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before treatment assignment to rule out acute cardiopulmonary events.

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

US trial sites

  • Research Site · Duarte, California
  • Research Site · Newport Beach, California
  • Research Site · Orange, California
  • Research Site · Santa Rosa, California
  • Research Site · Westwood, Kansas

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

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