Status:
RECRUITING
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.
Lead Sponsor:
Pfizer
Conditions:
Non-Small Cell Lung Cancer
Carcinoma, Non-Small-Cell Lung
Eligibility:
All Genders
18+ years
Phase:
PHASE3
Brief Summary
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 (NSCL...
Eligibility Criteria
Inclusion
- Participants must meet the following criteria:
- 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).
- 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.
- Large cell neuroendocrine carcinoma is excluded.
- Candidate for treatment with pembrolizumab monotherapy per local guidelines.
- Tumor has PD-L1 expression in ≥50% of tumor cells (TPS ≥50%) as determined by local testing
- Measurable disease based on RECIST v1.1 per investigator.
- 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
- Life expectancy of \<3 months in the opinion of the investigator.
- 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.
- 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.
- Known or suspected hypersensitivity, intolerance, or contraindication to any excipient contained in the drug formulation of sigvotatug vedotin or pembrolizumab.
- Participants with any of the following respiratory conditions:
- Evidence of noninfectious or drug-induced ILD or pneumonitis
- Known DLCO (adjusted for hemoglobin) \<50% predicted.
- Grade ≥3 pulmonary disease unrelated to underlying malignancy
- 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.
- 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.
- Receipt of a live vaccine within 30 days prior to first dose of study intervention.
- Pre-existing peripheral neuropathy Grade ≥2 per NCI CTCAE v5.0.
- 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.
- 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.
- History of autoimmune disease that has required systemic treatment in the past 2 years
- Participants with prior solid organ or bone marrow transplantation.
- 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.
- Prior and concomitant therapy:
- Any prior treatment with MMAE-derived drugs or IB6 targeting agents.
- 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.
- Prior radiotherapy to the lung within 6 months of first dose of study intervention, referencing the last date radiotherapy was received.
- 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.
- Any prior therapy with an immune-oncology agent directed to a stimulatory or co-inhibitory T-cell receptor
- History of or current ongoing infection, including participants positive for active HIV, HBV, or HCV.
- Severe uncontrolled cardiac or cerebrovascular condition within the previous 6 months
Key Trial Info
Start Date :
July 23 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
March 1 2029
Estimated Enrollment :
714 Patients enrolled
Trial Details
Trial ID
NCT06758401
Start Date
July 23 2025
End Date
March 1 2029
Last Update
March 12 2026
Active Locations (315)
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1
Providence St. Jude Medical Center Virginia K. Crosson Cancer Center and Infusion Center
Fullerton, California, United States, 92835
2
Providence St. Jude Medical Center
Fullerton, California, United States, 92835
3
St. Jude Heritage Medical Group - Fullerton Plaza Multi-Specialty Clinic (Pulmonary Function Test)
Fullerton, California, United States, 92835
4
Intermountain Health Lutheran Hospital
Golden, Colorado, United States, 80401