C5751003 - 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)

Studio Clinico

Patologia: Neoplasie del polmone

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Linee di trattamento: Non applicabile

Criteri di inclusione: 

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.

Criteri di esclusione: 

- 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.
    ◦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.

Numero di pazienti previsti: 

30

Schema di trattamento: 

Experimental: Sigvotatug Vedotin with Pembrolizumab
Participants will receive Sigvotatug Vedotin, administered as an IV infusion and pembrolizumab, administered as an IV infusion.

Active Comparator: Pembrolizumab Monotherapy
Participants will receive pembrolizumab, administered as an IV infusion.

Trattamento sperimentale: 

Sigvotatug Vedotin with Pembrolizumab

Trattamento di controllo: 

Pembrolizumab Monotherapy

Obiettivi primari dello studio: 

- Overall Survival
- Progression Free Survival (PFS) assessed by blinded independent central review (BICR)

Obiettivi secondari dello studio: 

- Progression Free Survival as assessed by Investigator
- Objective Response Rate as assessed by BICR
- Objective Response Rate as assessed by Investigator
- Duration of Response as assessed by BICR
- Duration of Response as assessed by Investigator
- Number of participants with adverse events (AEs)
- Pharmacokinetics (PK) of antibody-conjugated monomethyl auristatin E (ac-MMAE) in plasma: Plasma concentration at end of infusion (CEOI)
- PK of ac-MMAE in plasma: Plasma predose concentration (Cpredose)
- PK of unconjugated monomethyl auristatin E (MMAE) in plasma: Plasma concentration at end of infusion (CEOI)
- PK of MMAE in plasma: Plasma predose concentration (Cpredose)
- Number of participants with antidrug antibodies (ADAs).

Data di inizio dell'arruolamento: 20.01.2025

Data di fine dell'arruolamento: 07.02.2027

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2024-517968-36-00

Data di inserimento: 25.11.2025

Promotore

Pfizer

Principal Investigator ITALIA

Riferimento: Dr. Info non applicabile

Telefono: 00000

Email: na@na.it

Localita: na