PADL1NK-005 study design: a phase III trial of fetrastobart vedotin (Fetra-V) vs docetaxel in patients with previously treated tumor PD-L1–positive NSCLC

Fetrastobart vedotin (Fetra-V or PDL1V/PF-08046054) is an investigational antibody–drug conjugate that binds to programmed death ligand 1 (PD-L1)–expressing tumor cells and delivers a cytotoxic payload of monomethyl auristatin E. Fetra-V monotherapy has shown promising antitumor activity and manageable safety in patients with relapsed or refractory non-small cell lung cancer (NSCLC). PADL1NK-005 is a global, randomized, open-label phase III study assessing the efficacy and safety of Fetra-V monotherapy versus docetaxel in adults with PD-L1 ≥1% (utilizing locally tested PD-L1 expression using 22C3 or SP263 antibody clones) unresectable, locally advanced, or metastatic NSCLC following disease progression. Approximately 680 patients will be randomized 1:1 to receive Fetra-V 1.5 mg/kg using adjusted ideal body weight on days 1 and 8 of a 21-day cycle or docetaxel 75 mg/m2 on day 1 of a 21-day cycle. Randomization will be stratified by PD-L1 expression (1%–49% versus ≥50%), histology (nonsquamous versus squamous), select actionable genomic alterations (EGFR/ALK present versus absent/unknown), and Eastern Cooperative Oncology Group performance status (0 versus 1). The primary endpoint is overall survival in patients with PD-L1 ≥1% and PD-L1 ≥50%. Key secondary endpoints are progression-free survival and objective response rate by blinded independent central review in patients with PD-L1 ≥1% and PD-L1 ≥50%. NCT07144280 (https://clinicaltrials.gov/study/NCT07144280) Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. NSCLC can have high levels of a protein called programmed death ligand 1, or PD-L1. Many cancers use PD-L1 to hide from the immune system (body’s defense) to avoid being attacked and destroyed. Fetrastobart vedotin, or Fetra-V, is a new type of therapy called an antibody–drug conjugate consisting of an antibody that targets a specific protein, an anticancer drug, and a linker that connects the two. The antibody part of Fetra-V targets and attaches to PD-L1 on the surface of cancer cells. After Fetra-V enters the cancer cell, the linker releases the anticancer drug, killing the cancer cell. PADL1NK-005 is a clinical study investigating Fetra-V in people with NSCLC that has PD-L1, has spread beyond the lungs or cannot be removed by surgery, and has previously been treated with other drugs or no longer responds to therapy. The purpose of the study is to evaluate if Fetra-V increases the length of time that participants are alive after starting the study treatment (known as overall survival) compared with participants treated with the standard of care (a chemotherapy drug called docetaxel). Participants will also be monitored to see how long they live without the cancer getting worse (known as progression-free survival), if their cancer has shrunk or disappeared, and for side effects. Here we describe the design of the PADL1NK-005 study, including which participants will be included, how they will be treated, and how they will be monitored. A PDF version of this infographic is available as supplemental material.