TROP2-directed ADC

The key inclusion criteria^1-3 are –

• Age ≥18 years (if the legal age of consent is >18 years, then follow local regulatory requirements)
• Histologically documented NSCLC^a:
  – Stage IIIB/C NSCLC (not candidates for surgical resection or definitive chemoradiation) or Stage IV NSCLC^b 
  – Documented negative test results for EGFR, ALK, and ROS1 actionable genomic alterations
  – No known actionable genomic alterations in NTRK, BRAF, RET, MET, or other actionable driver kinases with locally approved therapies
• Formalin-fixed tumor tissue sample for the measurement of TROP2 protein expression and exploratory biomarkers
• Tumor with high PD-L1 expression (TPS ≥50%) as determined by PD-L1 IHC 22C3 pharmDx assay by central testing
• Measurable disease per RECIST v1.1
• ECOG PS of 0–1 at screening
• Life expectancy ≥3 months

^aPatients with squamous histology were eligible prior to Protocol Version 5.0. After Protocol Version 5.0, subjects with squamous histology are not eligible. Subjects with mixed histology, including those with a squamous component, remain eligible for the study even after Protocol Version 5.0.

^bClassification based on the American Joint Committee on Cancer, 8th edition.

References:

1. Study NCT05215340. ClinicalTrials.gov website.

2. Levy B, et al. Presented at ASCO Annual Meeting; June 3‒7, 2022; Chicago, IL. Abstract TPS3162.

3. Levy BP, et al. Future Oncology. 2023;19(21):1461-1472.

The key exclusion criteria^1-3 are –

• Prior systemic treatment for advanced/metastatic NSCLC
• Prior treatment with any of the following, including in the adjuvant/neoadjuvant setting:
  – Any agent (including ADC) containing a chemotherapeutic agent targeting topoisomerase I; TROP2-directed therapy; any anti–PD-1/PD-L1/PD-L2 agent or any agent directed to another stimulatory or co-inhibitory T-cell receptor; or any other ICI^a
• Spinal cord compression or active and untreated CNS metastases and/or carcinomatous meningitis^b
• Prior radiotherapy ≤4 weeks before start of study intervention or more than 30 Gy to the lung within 6 months of C1D1
• Current or history of (non-infectious) ILD/pneumonitis that required steroids, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
• Clinically severe pulmonary compromise resulting from intercurrent lung illnesses
• Uncontrolled or significant cardiovascular disease^c
• Clinically significant corneal disease
• Active, known, or suspected autoimmune disease
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy (>10 mg daily prednisone equivalent) or other immunosuppressive therapy ≤7 days prior to the first dose of study drug
• Active or uncontrolled hepatitis B/C or HIV
• Prior allogenic tissue/solid organ transplant

^aPatients who previously received neoadjuvant/adjuvant therapies other than those listed may be considered for enrollment if therapy was completed ≥6 months prior to the diagnosis of advance/metastatic disease.

^bPatients with previously treated brain metastases may participate provided they are radiographically eligible

^cDetails of uncontrolled or significant CV disease:

• Mean QTcF interval >470 ms regardless of sex (based on the average of the 12-lead electrocardiogram determination at screening).
• Myocardial infarction within 6 months prior to randomization.
• Uncontrolled angina pectoris within 6 months prior to randomization.
• LVEF <50% by ECHO or MUGA scan within 28 days before randomization.
• NYHA Class 2 to 4 CHF at screening.
• Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) within 28 days before randomization.