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Clinical Trial 21237

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT04644237

Phase: Phase II
Prinicipal Investigator: Saltos, Andreas

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Overview

Study Title

A Phase 2, Multicenter, Randomized Study of Trastuzumab Deruxtecan in Subjects with HER2-mutated Metastatic Non-Small Cell Lung Cancer (NSCLC) [DESTINY-Lung02]

Summary

This study was designed to evaluate the safety and efficacy of trastuzumab deruxtecan in HER2-mutated metastatic non-small cell lung cancer (NSCLC) participants who had disease recurrence or progression during/after at least one regimen of prior anticancer therapy (second line or later) that must have contained a platinum-based chemotherapy drug.

Objective

Primary Objectives To evaluate confirmed ORR of trastuzumab deruxtecan in HER2-mutated NSCLC subjects treated at 5.4 and 6.4 mg/kg doses. Secondary Objectives: To evaluate the clinical efficacy of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses by confirmed ORR by investigator assessment. To evaluate the clinical efficacy of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses by DoR. To evaluate further the clinical efficacy of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses by DCR, Progression-free survival (PFS) and Overall survival (OS). To evaluate safety of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses. To evaluate pharmacokinetics (PK) and immunogenicity of trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses. To assess symptoms, functioning and Healthrelated Quality of life (HRQoL) in subjects treated with trastuzumab deruxtecan at 5.4 and 6.4 mg/kg doses. To evaluate time to response (TTR) and best percent change in the sum of the diameters for all target lesions. To assess associations between biomarker status and efficacy and/or safety. To explore or assess: o Symptoms functioning and HRQoL with newly recommended NSCLC-SAQ. o The impact of treatment and disease state on health utility using the EQ-5D-5L. o Patient reported treatment tolerability. o The subject s overall impression of the severity of their cancer symptoms, change in condition since starting the study o The impact of treatment and disease on health care resource use.

Treatments

Therapies

Medications

DS-8201a (Trastuzumab Deruxtecan); Trastuzumab Deruxtecan ()

Inclusion Criteria

Inclusion Criteria:

  • Men or women 8 years of age or older
  • Pathologically documented metastatic NSCLC with a known activating HER2 mutation. Note: A HER2 mutation documented only from a liquid biopsy samples cannot be used for enrollment.
  • Had previous treatment (second line or later [2L+], including platinum therapy), not amenable to curative surgery or radiation
  • Presence of at least 1 measurable lesion confirmed by the blinded Independent Central Review based on RECIST version 1.1
  • Willing and able to provide an archival tumor tissue sample. A fresh biopsy is required if an archival tumor tissue sample cannot be supplied. Fine needle aspirates are not acceptable.
  • Eastern Cooperative Oncology Group performance status 0 to 1
  • Left ventricular ejection fraction ≥ 50% within 28 days before randomization
  • Adequate organ function as specified in protocol within 14 days before randomization
  • Adequate treatment washout period before randomization
  • Participants of reproductive/childbearing potential agree to use a highly effective form of contraception (or avoid intercourse) during study period and up to 7 months (females) and 4 months (males) after last study dose
  • Males should not freeze or donate sperm throughout the study period up to at least 4 months after last study dose; females should not donate or retrieve ova for their own use throughout the study period and up to at least 7 months after last study dose
  • Life expectancy 3 months or more

  • Exclusion Criteria

    Exclusion Criteria:

  • Known driver mutation in the epidermal growth factor receptor (EGFR) or BRAF gene or a known anaplastic lymphoma kinase (ALK) or ROS1 fusion
  • Medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above upper limit of normal at screening (as defined by the manufacturer) and without any myocardial infarction (MI)-related symptoms should have a cardiologic consultation before enrollment to rule out MI
  • Corrected QT interval (QTcF) prolongation > 470 msec (females) or >450 msec (males) based on average of the triplicate12-lead electrocardiogram at screening
  • History of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
  • 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
  • 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 participant's participation in the clinical study or evaluation of the clinical study results
  • Known human immunodeficiency virus (HIV) infection
  • Known active, clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C), based on available blood tests, liver ultrasound, or liver biopsy results
  • Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline
  • Pregnant, breastfeeding, or planning to become pregnant
  • Otherwise considered inappropriate for the study by the Investigator
  • Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg. pulmonary emboli within three months of the study randomization, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.)
  • Any autoimmune, connective tissue or inflammatory disorders (e.g., Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening
  • Prior complete pneumonectomy

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