Phase 3 Randomized Study of PF-08046054/SGN-PDL1V vs. Docetaxel in PD-L1 Positive Non-Small Cell Lung Cancer Patients

The primary objective is to compare overall survival between the experimental arm and the control arm in adults with previously treated non-small-cell lung cancer expressing programmed cell death ligand 1 (PD-L1) at levels ≥1% and ≥50%. This evaluation is clinically significant for determining the survival benefit of the investigational therapy compared to standard chemotherapy.

Secondary objectives include the following:

• Comparison of objective response rate as assessed by blinded independent central review (BICR) and by investigator.
• Evaluation of progression-free survival (PFS) via investigator assessment and BICR.
• Estimation of the duration of response (DOR) as assessed by both BICR and investigator.
• Characterization of the safety and tolerability profile of PF-08046054.
• Assessment of changes in quality of life (QoL), functioning, and lung cancer symptom response, including the time to definitive deterioration (TTdD).
• Characterization of the pharmacokinetics (PK) and immunogenicity of PF-08046054.

This study involves 434 participants diagnosed with non-small cell lung cancer. The study population includes both male and female patients within the age ranges corresponding to codes 3 and 4. Eligible individuals must have a histologically or cytologically confirmed diagnosis of locally advanced, unresectable Stage IIIB or IIIC, or metastatic Stage IV disease according to the AJCC and UICC staging systems. A requirement for participation is PD-L1 expression on ≥1% of tumor cells determined via immunohistochemistry. Participants may have known actionable genetic alterations, such as EGFR mutations or ALK translocations. The study objectives are:

• To compare overall survival between the experimental arm and the control arm in participants with tumor PD-L1 ≥1%.
• To compare overall survival in participants with tumor PD-L1 ≥50%.

This is a Phase 3, randomized, open-label study designed to evaluate the efficacy of PF-08046054/SGN-PDL1V compared to docetaxel in adults with previously treated non-small cell lung cancer (NSCLC). The primary objective is to compare overall survival (OS) between the experimental arm and the control arm. The study population includes participants with tumor PD-L1 expression of ≥1% or ≥50%. The research methodology involves intravenous infusion of either the test product, a humanised IgG1 monoclonal antibody against PD-L1 conjugated to monomethyl auristatin E via a valine-citrulline linker, or the comparator, docetaxel. Secondary endpoints include objective response rate (ORR), progression-free survival (PFS), duration of response (DOR), adverse events (AEs), and various quality of life (QoL) measures. The study is estimated to occur between December 2025 and December 2027.

The experimental treatment consists of a humanised IgG1 monoclonal antibody against PD-L1 conjugated to monomethyl auristatin E via a valine-citrulline linker. This substance is administered as a lyophilized powder for preparation for injection via intravenous infusion at a dosage of 1.5 mg/kg.

The comparator treatment is docetaxel. This agent is administered via intravenous infusion at a dosage of 75 mg/m2.

The primary efficacy endpoint is overall survival (OS). Secondary endpoints include objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR), which are evaluated using RECIST v1.1 as assessed by both the investigator and blinded independent central review (BICR).

Patient-reported outcomes are assessed through several instruments to evaluate quality of life (QoL). These include:

• Mean scores and changes from baseline in global health status, physical functioning, and role functioning using the EORTC QLQ-C30.
• Mean scores and changes from baseline in dyspnea, cough, and chest pain using the EORTC QLQ-LC13.
• Time to deterioration (TTdD) for global health status, physical functioning, role functioning, dyspnea, cough, and chest pain scores.

In the experimental arm, efficacy assessments also include the measurement of plasma concentration for both antibody-conjugated monomethyl auristatin E (ac-MMAE) and unconjugated MMAE at the end of infusion and predose. Additionally, the incidence of anti-drug antibodies (ADA) is monitored.