HERTHENA-Lung01: This Phase II trial is trying to understand the effectiveness of an immunotherapy (patritumab deruxtecan) in people with metastatic or locally advanced EGFR-mutated non-small cell lung cancerA Phase 2 Randomized Open-Label Study of Patritumab Deruxtecan (U3-1402) in Subjects With Previously Treated Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer (NSCLC)

Exclusion

Participants meeting any exclusion criteria for this study will be excluded from this study.

• Any previous histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy.
• Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening.

• Clinically severe respiratory compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:

  • Any underlying pulmonary disorder (eg, pulmonary emboli within 3 months prior to the study enrollment, severe asthma, severe chronic obstructive pulmonary disease [COPD]), restrictive lung disease, pleural effusion);
  • Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis); OR prior complete pneumonectomy.
• Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory or any form of immunosuppressive therapy prior to enrollment. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
• Evidence of any leptomeningeal disease.
• Evidence of clinically active spinal cord compression or brain metastases.

• Inadequate washout period prior to Cycle 1 Day 1, defined as:

  • Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days;
  • Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than EGFR TKI), <14 days or 5 half-lives, whichever is longer;
  • Monoclonal antibodies, other than immune checkpoint inhibitors, such as bevacizumab (anti-VEGF) and cetuximab (anti-EGFR) <28 days;
  • Immune checkpoint inhibitor therapy <21 days;
  • Major surgery (excluding placement of vascular access) <28 days;
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 days; or
  • Chloroquine or hydroxychloroquine <14 days.
• Prior treatment with an anti-human epidermal growth factor receptor 3 (HER3) antibody or single-agent topoisomerase I inhibitor.
• Prior treatment with an antibody drug conjugate (ADC) that consists of any topoisomerase I inhibitor
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, Grade ≤1 or baseline. Participants with chronic Grade 2 toxicities may be eligible at the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee.

• Has history of other active malignancy within 3 years prior to enrollment, except:

  • Adequately treated non-melanoma skin cancer;
  • Superficial bladder tumors (Ta, Tis, T1);
  • Adequately treated intraepithelial carcinoma of the cervix uteri;
  • Low risk non-metastatic prostate cancer (with Gleason score <7, and following local treatment or ongoing active surveillance);
  • Any other curatively treated in situ disease.
• Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1
• Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1.
• Participant with any human immunodeficiency virus (HIV) infection.