The Efficacy and Safety of Trastuzumab Deruxtecan in Advanced or Metastatic NSCLC With HER2 Over Expression

Inclusion criteria

• Male and female participants must be at least 18 years of age at the time of signing the ICF.
• Histologically documented Stage III locally advanced and unresectable non-squamous NSCLC not amenable to curative surgery or radiation and/or Stage IV NSCLC.
• Participants must have HER2 overexpression (IHC 3+).
• progressed following at least one or two prior systemic treatment.
• Prior anti-HER2 are eligible except for HER2 ADC.
• At least 1 measurable lesion by the investigator based on RECIST 1.1.
• LVEF ≥ 50% within 28 days before enrollment.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
• Adequate organ and bone marrow function within 14 days before enrolment. All parameters must be the most recent results available.
• Adequate treatment washout period before enrolment.
• Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner.

Exclusion criteria

• Has spinal cord compression or clinically active central nervous system metastases.
• Corrected QT interval (QTcF) prolongation to > 470 msec (females) or >450 msec (males) based on average of the screening triplicate12-lead ECG.
• History of (non-infectious) ILD / pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals
• Active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (HIV) infection or active hepatitis B (hepatitis B virus surface antigen or hepatitis B virus core antibody positive, at screening) or C infection.
• Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan.
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline.
• Known allergy or hypersensitivity to study treatment or any of the study drug excipients
• History of severe hypersensitivity reactions to other monoclonal antibodies.
• Pregnant or breastfeeding female participants, or participants who are planning to become pregnant.
• A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
• Any other clinically significant medical 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.