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)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Pfizer
- 入组人数
- 714
- 试验地点
- 554
- 主要终点
- Overall Survival
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •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
研究组 & 干预措施
Sigvotatug Vedotin with Pembrolizumab
Participants will receive Sigvotatug Vedotin, administered as an IV infusion and pembrolizumab, administered as an IV infusion.
干预措施: Pembrolizumab (Drug)
Sigvotatug Vedotin with Pembrolizumab
Participants will receive Sigvotatug Vedotin, administered as an IV infusion and pembrolizumab, administered as an IV infusion.
干预措施: Sigvotatug Vedotin (Drug)
Pembrolizumab Monotherapy
Participants will receive pembrolizumab, administered as an IV infusion.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Overall Survival
时间窗: Baseline to date of death from any cause (Approximately 2 years)
Overall survival defined as the duration from enrollment to death.
Progression Free Survival (PFS) assessed by blinded independent central review (BICR)
时间窗: From Baseline to to date of first documentation of progression OR death (Approximately 2 year)
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.
次要结局
- Progression Free Survival as assessed by Investigator(From Baseline to date of first progression or death (Approximately 4 Years))
- Objective Response Rate as assessed by BICR(From Baseline to to the date of progression OR death (approximately to 4 years))
- Objective Response Rate 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(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(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)(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)(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)(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)(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)(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)(Cycle 1 (up to Day 29), Cycle 3 Day 1, Cycle 5 Day 29, Cycle 8 Day 15 and Cycle 11 Day 1)