RecruitingNon-Small Cell Lung CancerCarcinoma, Non-Small-Cell LungCarcinoma, Non-Small-Cell Lung (NSCLC)

This is a Study to Learn About How the Combination of the Study Medicines Sigvotatug Vedotin Plus Pembrolizumab Works in People With Non-small Cell Lung Cancer With High Levels of PD-L1.

Eligible age

18+ yrs

Accepts

All genders

Locations

18 states

Healthy volunteers

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About this study

The purpose of the study is to compare how the new combination treatment (Sigvotatug Vedotin plus pembrolizumab) works compared to pembrolizumab alone in patients with non-small cell lung cancer (NSCLC) with high levels of PD-L1. This is a protein that acts as a kind of "brake" to keep the body's immune responses under control. The study is seeking for participants who: * Are confirmed to have NSCLC (Stage 3 or 4). * Have PD-L1 levels in more than 50% of the cancer cells. All participants in this study will receive pembrolizumab at the study clinic once every 6 weeks as an intravenous (IV) infusion (give directly into a vein). In addition, half of the participants will also receive Sigvotatug Vedotin once every 2 weeks as an IV infusion in addition to receiving pembrolizumab. Participants may receive pembrolizumab for up to about two years. Those participants taking Sigvotatug Vedotin can continue until their NSCLC is no longer responding. The study team will monitorsee how each participant is doing with the study treatment during regular visits at the clinic.

Sponsor: Pfizer

You may qualify if…

✓ 1. Participants must meet the following criteria:
✓ 1. Have pathologically confirmed Stage IIIB or IIIC NSCLC and not be a candidate for surgical resection or definitive chemoradiation, or Stage IV NSCLC per the AJCC Staging Manual (Version 8.0) and the UICC Staging System (Eighth edition).
✓ 2. Participants with non-squamous histology must have documented negative test results for EGFR, ALK, and ROS1 AGAs and no known AGAs in NTRK, BRAF, RET, MET, or other AGAs with approved front-line therapies per local standard of care.
✓ 3. Large cell neuroendocrine carcinoma is excluded.
✓ 4. Candidate for treatment with pembrolizumab monotherapy per local guidelines.
✓ 2. Tumor has PD-L1 expression in ≥50% of tumor cells (TPS ≥50%) as determined by local testing
✓ 3. Measurable disease based on RECIST v1.1 per investigator.
✓ 4. Resolution of acute effects of any prior therapy to either baseline severity or NCI CTCAE Grade 1 or less (except for AEs not constituting a safety risk in the investigator's judgment), unless otherwise excluded.

You may not qualify if…

✕ 1. Life expectancy of \<3 months in the opinion of the investigator.
✕ 2. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or make the participant inappropriate for the study.
✕ 3. Participants with any history of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
✕ 4. Known or suspected hypersensitivity, intolerance, or contraindication to any excipient contained in the drug formulation of sigvotatug vedotin or pembrolizumab.
✕ 5. Participants with any of the following respiratory conditions:
✕ 1. Evidence of noninfectious or drug-induced ILD or pneumonitis
✕ 2. Known DLCO (adjusted for hemoglobin) \<50% predicted.
✕ 3. Grade ≥3 pulmonary disease unrelated to underlying malignancy