The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.
Sigvotatug vedotin is an investigational compound. Its safety and efficacy have not been established
Active enrolling
United States, Belgium, Bulgaria, Czechia, France, Germany, Israel, Italy, Japan, Netherlands, Poland, South Korea, Spain, Taiwan
EXPERIMENTAL: Sigvotatug Vedotin with Pembrolizumab
Participants will receive Sigvotatug Vedotin, administered as an IV infusion and pembrolizumab, administered as an IV infusion.
DRUG: Sigvotatug Vedotin
MMAE-Antibody Drug Conjugate targeting Integrin Beta-6
DRUG: Pembrolizumab
Anti-PD-(L)1
ACTIVE_COMPARATOR: Pembrolizumab Monotherapy
Participants will receive pembrolizumab, administered as an IV infusion.
DRUG: Pembrolizumab
Anti-PD-(L)1
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.
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
Overall Survival
Overall survival defined as the duration from enrollment to death.
Baseline to date of death from any cause (Approximately 2 years)
Progression Free Survival (PFS) assessed by blinded independent central review (BICR)
Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression determined by blinded independent central review (BICR) assessment as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death due to any cause, whichever come first.
From Baseline to to date of first documentation of progression OR death (Approximately 2 year)
Progression Free Survival as assessed by Investigator
Progression Free Survival (PFS) is defined as the time from the date of first dose of study interventions to the date of first documentation of PD or death due to any cause, whichever occurs first.
From Baseline to date of first progression or death (Approximately 4 Years)
Objective Response Rate as assessed by BICR
Objective response rate is defined as the proportion of participants who have a confirmed CR or PR, as best overall response assessed by BICR as per RECIST 1.1, from the date of randomization to the date of disease progression, death due to any cause, whichever occurs first.
From Baseline to to the date of progression OR death (approximately to 4 years)
Objective Response Rate as assessed by Investigator
defined as the proportion of participants who achieve a best response of complete response (CR) or partial response (PR) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by Investigator.
From Baseline to to the date of progression OR death (approximately to 4 years)
Duration of Response as assessed by BICR
Duration of response is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined by BICR assessment as per RECIST 1.1 or death due to any cause, whichever occurs first.
From the date of the first objective response to the date of disease progression or death (approximately to 4 years)
Duration of Response as assessed by Investigator
defined time from the initial response (CR or PR) until documented tumor progression or death from any cause and based on Investigator assessment.
From the date of the first objective response to the date of disease progression or death (approximately to 4 years)
Number of participants with adverse events (AEs)
Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to \[study drug\] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.
From Baseline to end of treatment (up to 4 years)
Pharmacokinetics (PK) of antibody-conjugated monomethyl auristatin E (ac-MMAE) in plasma: Plasma concentration at end of infusion (CEOI)
To characterize the pharmacokinetics (PK) of sigvotatug vedotin when administered in combination with pembrolizumab
Cycle 1 (up to Day 29), Cycle 3 Day 1, Cycle 5 Day 29, Cycle 8 Day 15 and Cycle 11 Day 1
PK of ac-MMAE in plasma: Plasma predose concentration (Cpredose)
To characterize the pharmacokinetics (PK) of sigvotatug vedotin when administered in combination with pembrolizumab
Cycle 1 (up to Day 29), Cycle 3 Day 1, Cycle 5 Day 29, Cycle 8 Day 15 and Cycle 11 Day 1
PK of unconjugated monomethyl auristatin E (MMAE) in plasma: Plasma concentration at end of infusion (CEOI)
To characterize the pharmacokinetics (PK) of sigvotatug vedotin when administered in combination with pembrolizumab
Cycle 1 (up to Day 29), Cycle 3 Day 1, Cycle 5 Day 29, Cycle 8 Day 15 and Cycle 11 Day 1
PK of MMAE in plasma: Plasma predose concentration (Cpredose)
To characterize the pharmacokinetics (PK) of sigvotatug vedotin when administered in combination with pembrolizumab
Cycle 1 (up to Day 29), Cycle 3 Day 1, Cycle 5 Day 29, Cycle 8 Day 15 and Cycle 11 Day 1
Number of participants with antidrug antibodies (ADAs)
To characterize the immunogenicity of sigvotatug vedotin when administered in combination with pembrolizumab
Cycle 1 (up to Day 29), Cycle 3 Day 1, Cycle 5 Day 29, Cycle 8 Day 15 and Cycle 11 Day 1
714
Sponsor: Pfizer
Collaborator: None
For more information, call or email the Pfizer Clinical Trial Contact Center:
When calling, please reference this study number:
NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier.
NCT06758401
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