TROPION-LUNG08

Key outcome parameters

PFS and OS

Intervention

200 mg pembrolizumab & Dato-DXd  or pembrolizumab alone

Key inclusion criteria

Inclusion criteria:

• Had an allogenic tissue/solid organ transplant
  • Stage IIIB or IIIC disease and not candidates for surgical resection or definitive chemo radiation, or Stage IV NSCLC disease at the time of randomization
  • Documented negative test results for EGFR, ALK, and ROS1 actionable genomic alterations based on analysis of tumor tissue. If test results for EGFR, ALK, and ROS1 are not available, subjects are required to undergo testing performed locally for these genomic alterations.
  • No known actionable genomic alterations in NTRK, BRAF, RET, MET, or other actionable driver kinases with locally approved therapies. (Testing for genomic alterations besides EGFR, ALK, and ROS1 is not required prior to enrollment). Subjects with squamous NSCLC are only required to undergo EGFR, ALK, and ROS1 testing if they have no history of tobacco smoking or were diagnosed with NSCLC at <40 years of age.
• Subjects whose tumors harbor KRAS mutations are eligible for the study.
• Tumor has high PD-L1 expression (TPS ≥50%) as determined by PD-L1 IHC 22C3 pharmDx assay by central testing (minimum of 6 slides).
• Has provided a formalin-fixed tumor tissue sample (minimum of 10 [preferably 15] × 4-micron sections or block equivalent) for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers. This tissue requirement is in addition to the tissue required for PD-L1 testing for tissue screening purposes.
• Has left ventricular ejection fraction (LVEF) ≥50% by either an echocardiogram (ECHO)or multigated acquisition scan (MUGA) within 28 days before randomization.
• ECOG PS of 0 or 1 at screening

Key exclusion criteria

Exclusion criteria:

• Has received prior systemic treatment for advanced/metastatic NSCLC
• Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting:
  • Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I
  • TROP2-targeted therapy
  • Any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137)
  • Any other ICIs
• Subjects who received adjuvant or neoadjuvant therapy OTHER than those listed above, are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced or metastatic disease
• A computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the brain at baseline (MRI preferred) is required for all subjects
• Has received prior radiotherapy ≤4 weeks of start of study intervention or more than 30Gy to the lung within 6 months of Cycle 1 Day 1
• History of another primary malignancy (beyond NSCLC) except for:
  • Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study treatment and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression and who in the opinion of the Investigator are not deemed to require active intervention
• Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study treatment and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease.
• Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression and who in the opinion of the Investigator are not deemed to require active intervention.
• Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) within 28 days before randomization.
• Significant corneal disease.
• Had an allogeneic tissue/solid organ transplant