Study on Zelenectide Pevedotin for Advanced or Metastatic Non-Small Cell Lung Cancer with NECTIN4 Amplification

Key Inclusion Criteria

• Histologically or cytologically confirmed advanced or metastatic NSCLC.

  1. Cohort A: Histologically or cytologically confirmed non-squamous NSCLC.
  2. Cohort B: Histologically or cytologically confirmed squamous NSCLC.

• Confirmed NECTIN4 gene amplification by an analytically validated clinical trial assay.

• Participants must not have received more than 3 prior lines of systemic therapy in the advanced/metastatic setting.

  • Participants with no known actionable genomic alterations must have received both platinum based therapy and immunotherapy given either sequentially or in combination for advanced/metastatic NSCLC.
  • Those with known actionable genomic alterations (eg, EGFR, ALK, BRAF, MET, ROS1, NTRK1/2/3, RET) are eligible provided they have received or are not candidates for available standard targeted therapy in the advanced/metastatic setting.

• Measurable disease as defined by RECIST v1.1.

• Adequate archival or fresh tumor tissue comprised of advanced or metastatic NSCLC should be available for submission to central laboratory, if not provided during prescreening.

• Life expectancy ≥ 12 weeks.

• Eastern Cooperative Oncology Group Performance Status of ≤ 1.

Key Exclusion Criteria

• Evidence of mixed small cell lung cancer (SCLC) and NSCLC histology.
• Prior treatment with monomethyl auristatin E (MMAE) (vedotin) based therapy.
• Known hypersensitivity or allergy to any of the ingredients of any of the study interventions, or to MMAE.
• Ongoing clinically significant toxicity (Grade ≥ 2) associated with prior treatment for NSCLC (including radiotherapy or surgery), with the exception of well-controlled immuno-oncology related endocrine disorders on supportive or replacement therapy, and alopecia.
• Active keratitis or corneal ulcerations.
• Active or untreated central nervous system (CNS) metastases.
• Uncontrolled diabetes or hypertension.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent draining procedures (monthly or more frequently).
• Active interstitial lung disease or pneumonitis requiring ongoing treatment with steroids (>10mg/day of prednisone or equivalent) or other immunosuppressive medications; or any prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids.
• History or another active malignancy that would interfere with the safety or efficacy evaluation of the clinical study.
• Requirement, while on study, for treatment with strong inhibitors or strong inducers of human cytochrome P450 3A ([cytochrome P450 3A] CYP3A) or inhibitors of P-glycoprotein (P-gp) including herbal- or food-based inhibitors.
• Prior treatment with any systemic anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to first dose of study treatment.

Note: Additional protocol defined Inclusion/Exclusion criteria apply