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.
Recruiting · NCT06758401 · Interventional (participants receive a specific treatment) · Lead sponsor: Pfizer
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
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.
Who can take part
Age range
18 Years and older
Sex
All (male and female)
Healthy volunteers
No - a diagnosis or condition is required
Phase
Phase 3
Study type
Interventional (participants receive a specific treatment)
Inclusion criteria
- 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 criteria
- 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
Where it is running
60 locations listed across 18 US states.
- Providence Medical Foundation - Fullerton, California, United States
- Providence St. Jude Medical Center Virginia K. Crosson Cancer Center and Infusion Center - Fullerton, California, United States
- St. Jude Heritage Medical Group - Fullerton Plaza Multi-Specialty Clinic (Pulmonary Function Test) - Fullerton, California, United States
- Intermountain Health Cancer Center Lutheran Hospital - Golden, Colorado, United States
- Cancer Centers of Colorado St. Mary's Regional Hospital - Grand Junction, Colorado, United States
- Intermountain Health St. Mary's Regional Hospital - Grand Junction, Colorado, United States
- Intermountain Health - Grand Junction, Colorado, United States
- Intermountain Health Lutheran Hospital - Wheat Ridge, Colorado, United States
- Washington DC Veterans Affairs Medical Center - Washington D.C., District of Columbia, United States
- Mid Florida Hematology and Oncology Center - Orange City, Florida, United States
- BRCR Global - Plantation, Florida, United States
- Endeavor Health - Elmhurst, Illinois, United States
- Hope and Healing Cancer Services - Hinsdale, Illinois, United States
- Endeavor Health - Naperville, Illinois, United States
- Hope and Healing Cancer Services - New Lenox, Illinois, United States
- Saint Luke's South Hospital - Overland Park, Kansas, United States
- Maine Medical Center - Portland, Maine, United States
- MaineHealth Cancer Care - Scarborough - Scarborough, Maine, United States
- MaineHealth Cancer Care and Blood Disorders Scarborough - Scarborough, Maine, United States
- Southcoast Centers for Cancer Care - Fairhaven, Massachusetts, United States
- Southcoast Centers for Cancer Care - Fall River, Massachusetts, United States
- Corewell Health - Butterworth Hospital - Grand Rapids, Michigan, United States
- Corewell Health - Lemmen Holton Cancer Pavilion - Grand Rapids, Michigan, United States
- Corewell Health - Research Specimen Processing Area - Grand Rapids, Michigan, United States
- Corewell Health Investigational Drug Services - Grand Rapids, Michigan, United States
- Corewell Health - Grand Rapids, Michigan, United States
- Minnesota Oncology Hematology, PA - Burnsville, Minnesota, United States
- Minnesota Oncology Hematology PA - Coon Rapids, Minnesota, United States
- M Health Fairview Cancer Clinic-Edina - Edina, Minnesota, United States
- Minnesota Oncology Hematology PA - Edina, Minnesota, United States
- Minnesota Oncology Hematology PA - Maple Grove, Minnesota, United States
- M Health Fairview St. John's Hospital - Maplewood, Minnesota, United States
- Minnesota Oncology Hematology PA - Maplewood, Minnesota, United States
- Hennepin County Medical Center - Minneapolis, Minnesota, United States
- North Memorial Health Cancer Center - Robbinsdale, Minnesota, United States
- Metro Minnesota Community Oncology Research Consortium (MMCORC) - Saint Louis Park, Minnesota, United States
- Park Nicollet Frauenshuh Cancer Center - Saint Louis Park, Minnesota, United States
- Regions Hospital - Saint Paul, Minnesota, United States
- Minnesota Oncology Hematology, P.A. Cornerstone Medical Specialty Center - Woodbury, Minnesota, United States
- Jackson Oncology Associates, PLLC - Jackson, Mississippi, United States
- Jackson Oncology Associates, PLLC - Jackson, Mississippi, United States
- Saint Luke's Cancer Institute - Kansas City, Missouri, United States
- Saint Luke's Hospital of Kansas City - Kansas City, Missouri, United States
- Saint Luke's East Hospital - Lee's Summit, Missouri, United States
- Oncology Hematology West, PC dba Nebraska Cancer Specialists - Fremont - Fremont, Nebraska, United States
- Oncology Hematology West, PC dba Nebraska Cancer Specialists - Grand Island - Grand Island, Nebraska, United States
- Oncology Hematology West, PC dba Nebraska Cancer Specialists - Regional - Grand Island, Nebraska, United States
- Cancer Partners of Nebraska - Lincoln, Nebraska, United States
- Oncology Hematology West P.C. dba Nebraska Cancer Specialists - Methodist - Omaha, Nebraska, United States
- Oncology Hematology West, PC dba Nebraska Cancer Specialists - Bergan - Omaha, Nebraska, United States
- Oncology Hematology West P.C. dba Nebraska Cancer Specialists - Omaha, Nebraska, United States
- Hematology Oncology Associates of Rockland - Nyack, New York, United States
- Brody School of Medicine at East Carolina University - Greenville, North Carolina, United States
- ECU Health Medical Center - Greenville, North Carolina, United States
- Carolina Cancer Research Center - Wilson, North Carolina, United States
- University Hospitals Seidman Cancer Center at UH Avon Health Center - Avon, Ohio, United States
- Gabrail Cancer Center Research - Canton, Ohio, United States
- University Hospitals Cleveland Medical Center - Cleveland, Ohio, United States
- University Hospitals Seidman Cancer Center at UH Mentor Health Center - Mentor, Ohio, United States
- UH Minoff Health Center at Chagrin Highlands - Orange, Ohio, United States
Showing 60 of 372 listed sites. See the official record for the complete list.
Read the full protocol, contacts and eligibility on ClinicalTrials.gov →