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.
Official title: AN OPEN-LABEL, RANDOMIZED, CONTROLLED PHASE 3 STUDY OF SIGVOTATUG VEDOTIN IN COMBINATION WITH PEMBROLIZUMAB COMPARED WITH PEMBROLIZUMAB MONOTHERAPY AS FIRST-LINE TREATMENT IN PARTICIPANTS WITH PD-L1 HIGH (≥50% OF TUMOR CELLS EXPRESSING PD-L1), LOCALLY ADVANCED, UNRESECTABLE, OR METASTATIC NON-SMALL CELL LUNG CANCER
Is NCT06758401 recruiting? Yes, currently enrolling (Oct 2026). This Phase 3 trial studies multiple treatments including Sigvotatug Vedotin and Pembrolizumab for non-small cell lung cancer.
Treatment: Sigvotatug Vedotin · Pembrolizumab — 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.
Check if I qualifyExtracted eligibility criteria
Treatments studied
Immunotherapy
Other
Cancer type
Non-Small Cell Lung Carcinoma
Biomarker criteria
Required: PD-L1 (CD274) overexpression (≥50% of tumor cells (TPS ≥50%))
Tumor has PD-L1 expression in ≥50% of tumor cells (TPS ≥50%) as determined by local testing.
Excluded: EGFR actionable genomic alteration
Participants with known AGAs including EGFR ... for which there are approved and available first-line therapies per local SOC are ineligible. Documented negative results for EGFR ... AGAs are required for participants with non-squamous histology.
Excluded: ALK actionable genomic alteration
Participants with known AGAs including ... ALK ... for which there are approved and available first-line therapies per local SOC are ineligible. Documented negative results for ... ALK ... AGAs are required for participants with non-squamous histology.
Excluded: ROS1 actionable genomic alteration
Participants with known AGAs including ... ROS1 ... for which there are approved and available first-line therapies per local SOC are ineligible. Documented negative results for ... ROS1 ... AGAs are required for participants with non-squamous histology.
Excluded: NTRK1 actionable genomic alteration
Participants with known AGAs including ... NTRK ... for which there are approved and available first-line therapies per local SOC are ineligible.
Excluded: NTRK2 actionable genomic alteration
Participants with known AGAs including ... NTRK ... for which there are approved and available first-line therapies per local SOC are ineligible.
Excluded: NTRK3 actionable genomic alteration
Participants with known AGAs including ... NTRK ... for which there are approved and available first-line therapies per local SOC are ineligible.
Excluded: BRAF actionable genomic alteration
Participants with known AGAs including ... BRAF ... for which there are approved and available first-line therapies per local SOC are ineligible.
Excluded: RET actionable genomic alteration
Participants with known AGAs including ... RET ... for which there are approved and available first-line therapies per local SOC are ineligible.
Excluded: MET actionable genomic alteration
Participants with known AGAs including ... MET ... for which there are approved and available first-line therapies per local SOC are ineligible.
Disease stage
Required: Stage IIIB, IIIC, IV
Performance status
WHO 0–1
Prior therapy
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 for locally advanced, unresectable, or metastatic NSCLC
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 Medical Foundation · Fullerton, California
- 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 Cancer Center Lutheran Hospital · Golden, Colorado
Showing up to 5 US sites.
See all sites on ClinicalTrials.gov →Frequently asked questions
Is NCT06758401 currently recruiting?
Yes, this trial is currently recruiting patients.
Are there prior therapy exclusions?
Yes. Prior MMAE-derived drug, IB6 targeting agent, systemic therapy for locally advanced, unresectable, or metastatic NSCLC disqualifies patients from enrollment.
Does this trial require CD274?
Yes, CD274 overexpression is a required biomarker for enrollment.
Are patients with EGFR alterations eligible?
No. EGFR actionable genomic alteration is an exclusion criterion.
Are patients with ALK alterations eligible?
No. ALK actionable genomic alteration is an exclusion criterion.
What disease stage is eligible?
Stage IIIB or IIIC or IV is required.
Could you qualify for this trial?
Enter your biomarker results to see how this trial's eligibility criteria match your specific cancer profile.
Check if I qualify