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Clinical Trial 19743

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT03505710

Phase: Phase II
Prinicipal Investigator: Andreas Saltos

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Study Title

A Phase 2, Multicenter, Open-Label, 2-Cohort Study Of Trastuzumab Deruxtecan (DS-8201a), An Anti-HER2 Antibody Drug Conjugate (ADC), For HER2-Over-Expressing Or -Mutated, Unresectable And/Or Metastatic Non-Small Cell Lung Cancer (NSCLC)


The primary objective of this trial is to evaluate the efficacy of trastuzumab deruxtecan in HER2-over-expressing and/or HER2-mutated advanced NSCLC subjects.


Primary Objective: The primary objective is to evaluate the objective response rate (ORR) of trastuzumab deruxtecan in HER2-overexpressing and/or HER2 mutated advanced NSCLC subjects. The secondary objectives are: To evaluate duration of response (DoR),disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) To further evaluate the safety of trastuzumab deruxtecan To determine the pharmacokinetics (PK) of trastuzumab deruxtecan




Trastuzumab Deruxtecan ()

Inclusion Criteria

  • Must have provided informed consent for study participation before performance of any study-specific procedures or test.
  • Age 18 or older
  • Pathologically documented unresectable and/or metastatic non-squamous NSCLC
  • Has relapsed from or is refractory to standard treatment or for which no standard treatment is available
  • For Cohort 1 only: HER2-overexpression (IHC 2+ or 3+) status must be assessed and confirmed by Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory or equivalent, from an archival tumor tissue sample
  • For Cohort 2 only: Documented any known activating HER2 mutation from an archival tumor tissue sample analyzed by CLIA laboratory or equivalent
  • Presence of at least 1 measurable lesion assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Is willing and able to provide an adequate archival tumor tissue sample. Fine needle aspirates are not acceptable.
  • Is willing to undergo a tissue biopsy, after the completion of the most recent treatment regimen
  • Has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1
  • Adequate organ function as defined per protocol.
  • Adequate treatment washout period before enrollment, as defined per protocol.
  • Patients of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 4.5 months for males and at least 7 months for females after the last dose of study drug.
  • Males must not freeze or donate sperm starting at screening and throughout the study period, and at least 4.5 months after final study drug administration. Preservation of sperm should be considered prior to enrollment in this trial.
  • Females must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period and for at least 7 months after final study drug administration.

  • Exclusion Criteria

  • Previously treated with HER2-targeted therapies, except for pan-HER class tyrosine kinase inhibitors.
  • For Cohort 1 only: Has known HER2 mutation. 3. Uncontrolled or significant cardiovascular disease, specifics outlined per protocol.
  • Has a history of (non-infectious) interstitial lung disease (ILD) that required steroids, has current ILD, or where suspected ILD cannot be ruled out by imaging at screening.
  • Has clinically significant corneal disease in the opinion of the Investigator.
  • Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.
  • Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated.
  • History of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product.
  • History of severe hypersensitivity reactions to other monoclonal antibodies.
  • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
  • Substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject’s participation in the clinical study or evaluation of the clinical study results.
  • Known HIV infection, or active hepatitis B or C infection. Subjects should be tested for HIV prior to enrollment if required by local regulations or institutional review board (IRB)/ethics committee (EC).
  • Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to less than Grade 1 or baseline. Patients with chronic grade 2 toxicities may be eligible per the discretion of the investigator after consultation with the sponsor medical monitor or designee.
  • Female patients who are pregnant or breastfeeding or planning to become pregnant.
  • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.) and any autoimmune connective tissue or inflammatory disorders with potential pulmonary involvement (i.e., Rheumatoid arthritis, Sjogren's sarcoidosis, etc) or prior pneumonectomy.
  • Prior treatment with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor.
  • Social, familial, or geographical factors that would interfere with study participation or follow-up.
  • Has a concomitant medical condition that would increase the risk of toxicity, in the opinion of the investigator.
  • Patient must not be a family member of the study site personnel or of the Sponsor personnel.
  • Otherwise considered inappropriate for the study by the investigator.

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