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OncoMatch/Clinical Trials/NCT06758401

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.

Is NCT06758401 recruiting? Yes, currently enrolling (May 2026). This Phase 3 trial studies multiple treatments including Sigvotatug Vedotin and Pembrolizumab for non-small cell lung cancer.

Phase 3RecruitingPfizerNCT06758401Data as of May 2026

Treatment: Sigvotatug Vedotin · PembrolizumabThe 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.

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Extracted eligibility criteria

Cancer type

Non-Small Cell Lung Carcinoma

Biomarker criteria

Required: EGFR wild-type

documented negative test results for EGFR ... AGAs

Required: ALK wild-type

documented negative test results for ... ALK ... AGAs

Required: ROS1 wild-type

documented negative test results for ... ROS1 AGAs

Required: NTRK1 wild-type

no known AGAs in NTRK, BRAF, RET, MET, or other AGAs with approved front-line therapies

Required: NTRK2 wild-type

no known AGAs in NTRK, BRAF, RET, MET, or other AGAs with approved front-line therapies

Required: NTRK3 wild-type

no known AGAs in NTRK, BRAF, RET, MET, or other AGAs with approved front-line therapies

Required: BRAF wild-type

no known AGAs in NTRK, BRAF, RET, MET, or other AGAs with approved front-line therapies

Required: RET wild-type

no known AGAs in NTRK, BRAF, RET, MET, or other AGAs with approved front-line therapies

Required: MET wild-type

no known AGAs in NTRK, BRAF, RET, MET, or other AGAs with approved front-line therapies

Required: PD-L1 (CD274) overexpression (TPS ≥50%)

Tumor has PD-L1 expression in ≥50% of tumor cells (TPS ≥50%) as determined by local testing

Disease stage

Required: Stage IIIB, IIIC, IV

Performance status

WHO 0–1

Prior therapy

No prior treatment (treatment-naive required)
Max 0 prior lines

Cannot have received: MMAE-derived drug

Any prior treatment with MMAE-derived drugs or IB6 targeting agents.

Cannot have received: IB6 targeting agent

Any prior treatment with MMAE-derived drugs or IB6 targeting agents.

Cannot have received: systemic therapy

Exception: Neo(adjuvant) anti-PD-(L)1 is allowed if recurrence or progression occurred ≥9 months after the last dose. Other (neo)adjuvant or definitive therapy is allowed if recurrence or progression occurred ≥6 months after the last dose.

Prior systemic therapy, including anti-PD-(L)1 therapy, for locally advanced, unresectable, or metastatic NSCLC.

Cannot have received: immune-oncology agent directed to a stimulatory or co-inhibitory T-cell receptor

Any prior therapy with an immune-oncology agent directed to a stimulatory or co-inhibitory T-cell receptor

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • Providence St. Jude Medical Center Virginia K. Crosson Cancer Center and Infusion Center · Fullerton, California
  • Providence St. Jude Medical Center · Fullerton, California
  • St. Jude Heritage Medical Group - Fullerton Plaza Multi-Specialty Clinic (Pulmonary Function Test) · Fullerton, California
  • Intermountain Health Lutheran Hospital · Golden, Colorado
  • lntermountain Health Cancer Center at Lutheran · Golden, Colorado

Showing up to 5 US sites. See all sites on ClinicalTrials.gov →

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