Trastuzumab Deruxtecan in Participants With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC)
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Trastuzumab deruxtecan
Intervention description: Trastuzumab deruxtecan 100 mg will be provided as a sterile lyophilized powder and reconstituted with 5 mL water for injection (final concentration 20 mg/mL [ie, 100 mg/5 mL]). The study drug will be administered as an intravenous (IV) infusion over 30 to 90 min Q3W ± 2 days. The initial dose of study drug will be infused for 90 ± 10 min.
Intervention MeSH terms: Trastuzumab; Trastuzumab deruxtecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 152.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-small Cell Lung Cancer; Trastuzumab Deruxtecan

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent

          -  Men or women ≥18 years, follow local regulatory requirements if the legal age of the
             consent for study participation is >18 years

          -  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 including platinum therapy in the metastatic/locally advanced
             setting and not amenable to curative surgery or radiation. Participant must have
             progressed during or after the last treatment regimen or discontinued because of
             unacceptable toxicity.

          -  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. Resection and core
             needle biopsy are acceptable. Fine needle aspirates or cell block are not acceptable.

          -  Eastern Cooperative Oncology Group performance status 0 to 1

          -  Left ventricular ejection fraction ≥ 50% within 28 days before randomization Resection
             and core needle biopsy are acceptable - 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:

          -  Known driver mutation in the epidermal growth factor receptor (EGFR), BRAF, or MET
             exon 14 gene or a known anaplastic lymphoma kinase (ALK), ROS1, RET, or NTRK 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 randomization 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) such as those with serologic evidence of viral infection within 28 days
             of Cycle 1, Day 1

          -  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

          -  Had prior treatment with any agent, including an antibody drug conjugate (ADC),
             containing a chemotherapeutic agent targeting topoisomerase I