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Combining Sigvotatug Vedotin and Pembrolizumab for Non-Small Cell Lung Cancer

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 (BE6A LUNG-02)

Phase 3 Interventional Pfizer · NCT06758401

This study is testing a new combination of two treatments, Sigvotatug Vedotin and pembrolizumab, to see if it helps people with advanced non-small cell lung cancer feel better compared to just using pembrolizumab alone.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment714 (estimated)
Ages18 Years and up
SexAll
SponsorPfizer Industry-sponsored
Drugs / interventionspembrolizumab, Chemotherapy, immunotherapy, prednisone
Locations329 sites (Fullerton, California and 328 other locations)
Trial IDNCT06758401 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of a new combination treatment of Sigvotatug Vedotin and pembrolizumab compared to pembrolizumab alone in patients with non-small cell lung cancer (NSCLC) that has high levels of PD-L1. Participants will receive pembrolizumab every six weeks, while half of them will also receive Sigvotatug Vedotin every two weeks. The study focuses on patients with Stage IIIB, IIIC, or IV NSCLC who are not candidates for surgery or definitive chemoradiation. The goal is to determine how well this combination therapy works in improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults with confirmed Stage IIIB, IIIC, or IV NSCLC and PD-L1 expression in 50% or more of their tumor cells.

Not a fit: Patients with non-squamous histology who have positive test results for EGFR, ALK, or ROS1 mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with advanced non-small cell lung cancer.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy combinations, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

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.

Exclusion Criteria:

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
6. Known active CNS lesions are excluded. Participants with definitively treated brain metastases (surgery and/or radiotherapy) may be eligible. Clinically inactive brain metastases of longest diameter \<0.5 cm are permitted.
7. Major surgery (defined as a surgery requiring inpatient hospitalization of at least 48 hours) within 21 days or minor surgery within 7 days prior to first dose of study intervention.
8. Receipt of a live vaccine within 30 days prior to first dose of study intervention.
9. Pre-existing peripheral neuropathy Grade ≥2 per NCI CTCAE v5.0.
10. Uncontrolled diabetes mellitus, defined as HbA1c ≥8.0% or HbA1c between 7.0% and 8.0% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
11. Prior immune-related AE that led to anti-PD-(L)1 treatment discontinuation, required a high-dose steroid taper (≥0.5 mg/kg prednisone or equivalent per day) for \>2 weeks, or required treatment with systemic immunosuppressive therapy.
12. History of autoimmune disease that has required systemic treatment in the past 2 years
13. Participants with prior solid organ or bone marrow transplantation.
14. Currently receiving a high-dose steroid (\>10 mg prednisone or equivalent per day) or other immune suppressant or has a condition requiring a chronic high-dose steroid or immune suppressant.
15. Prior and concomitant therapy:

    1. Any prior treatment with MMAE-derived drugs or IB6 targeting agents.
    2. Prior systemic therapy, including anti-PD-(L)1 therapy, for locally advanced, unresectable, or metastatic NSCLC.

       * (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.
    3. Prior radiotherapy to the lung within 6 months of first dose of study intervention, referencing the last date radiotherapy was received.
    4. Chemotherapy, biologics, and/or other antitumor treatment with immunotherapy not specifically prohibited that is completed less than 4 weeks prior to first dose of study intervention, or 2 weeks for palliative radiotherapy.
    5. Any prior therapy with an immune-oncology agent directed to a stimulatory or co-inhibitory T-cell receptor
16. History of or current ongoing infection, including participants positive for active HIV, HBV, or HCV.
17. Severe uncontrolled cardiac or cerebrovascular condition within the previous 6 months

Where this trial is running

Fullerton, California and 328 other locations

+279 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-Small Cell Lung CancerCarcinoma, Non-Small-Cell LungLung Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.