This is an international, multicenter, randomized, parallel-group, open-label, active-controlled phase 3 trial comparing the efficacy and safety of acasunlimab in combination with pembrolizumab versus docetaxel in subjects with Stage 4 PD-L1-positive metastatic NSCLC (PD-L1 ≥1%) who have been treated with PD-1/PD-L1 inhibitor and platinum-containing chemotherapy, administered either in combination or sequentially.

Subjects will be randomized 1:1 to receive either:

• Acasunlimab and pembrolizumab
• Docetaxel 75 mg/m² Q3W

Determine the clinical efficacy of acasunlimab in combination with pembrolizumab versus docetaxel as second-/third-line therapy in metastatic NSCLC after PD1/PD-L1-inhibitor-containing standard of care.

Subject has histologically or cytologically confirmed metastatic NSCLC (Stage 4) and:

• Progressed on 1 prior line of therapy (PD-1/PD-L1 inhibitor and platinum-based chemotherapy concomitantly) or no more than 2 prior lines of therapy (PD-1/PD-L1 inhibitor and platinum-based chemotherapy sequentially and irrespective of the order) in the metastatic disease setting.
• Has had clinical benefit defined as documented radiographic SD or better on last
  prior PD-1/PD-L1 inhibitor-containing regimen.
• Positive tumor PD-L1 expression (tumor cells ≥1%)
• Subject has measurable disease according to RECIST v1.1 as assessed by the investigator.
• Subject must have ECOG performance status ≤ 1.
• Subject has a life expectancy of ≥3 months.
• Subject must have adequate organ and bone marrow function.

• Documented EGFR/ALK/ROS1/RET negative. KRAS+/BRAF allowed if targeted therapy is not available locally.
• Brain mets should be treated and stable for >28 days prior treatment with docetaxel for NSCLC.
• Prior re-treatment with antiPD-1/PD-L1 mAb in the metastatic setting unless the treatment duration of the last prior antiPD-1/PD-L1 mAb was of at least 6 months.
• Treatment with an anti-cancer agent within 28 days prior to investigational medicinal product administration.