A Randomized, Double-Blind, Placebo-Controlled Trial of Tomivosertib in Combination With Anti-PD-(L)1 Therapy in Subjects With NSCLC as First Line Therapy or When Progressing on Single-Agent First-Line Anti PD (L)1 Therapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 68
- 试验地点
- 140
- 主要终点
- To characterize the PFS of tomivosertib when added to pembrolizumab and pemetrexed in non-squamous NSCLC, and pembrolizumab in squamous NSCLC as first line maintenance therapy.
研究概览
简要总结
Tomivosertib combined with pembrolizumab in Subjects with PD-L1 positive NSCLC
详细描述
A Randomized, Double-Blind, Placebo-Controlled Trial of Tomivosertib in Combination With Anti-PD-(L)1 Therapy in Subjects With Non-Small Cell Lung Cancer as First Line Therapy or When Progressing on Single-Agent First-Line Anti PD (L)1 Therapy
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
In all cohorts, investigational product (IP, tomivosertib or placebo) will be blinded and pembrolizumab will be open label. On Cohort C, pembrolizumab and pemetrexed will be open label.
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
- •Inclusion Criteria for Cohort A: Subjects who meet all of the following criteria will be eligible to participate in Cohort A of the study:
- •Have initiated first-line therapy for NSCLC with pembrolizumab and satisfy the following:
- •Have tumor PD-L1 ≥1% by 22C3 IHC;
- •Are judged by the Principal Investigator as tolerating pembrolizumab monotherapy; and
- •Have been on pembrolizumab for at least 3 months (measured from actual first dose date to first dose date of the current study) and the most recent scans are the first scans to objectively demonstrate Progressive Disease per RECIST 1.1
- •The first scan conducted a minimum of 21 days after first dose of anti-PD-(L)1 therapy must have shown either SD, PR, or CR (ie, not Progressive Disease) per RECIST 1.1; and
- •The 2 most recent scans (including 1 demonstrating Progressive Disease) are available to be reviewed
- •Inclusion Criterion for Cohort B
- •Subjects who meet the following criterion will be eligible to participate in Cohort B of the study:
- •Are eligible for single-agent pembrolizumab for advanced/metastatic NSCLC in accordance with the package insert and have tumor PD-L1 ≥50% by 22C3 IHC
- •Must not have been treated previously with platinum-based chemotherapy in the advanced/metastatic setting. Note: Subjects may have received chemotherapy and/or anti PD (L)1 therapy in the neo/adjuvant setting, provided the last dose of therapy was >9 months prior to randomization.
- •All cohorts require PD-L1 testing (TPS as determined by an FDA-approved test: subjects in Cohort B must specifically have PD-L1 testing using the PD-L1 IHC 22C3 pharmDx test kit). Subjects in Cohort B for whom PD-L1 testing was not performed with the required IHC 22C3 pharmDx test kit may be randomized if all other study criteria have been met, pending retest with the required IHC 22C3 pharmDx test kit.
- •Subjects who meet the following criterion will be eligible to participate in Cohort C of the study:
- •Have initiated IL therapy for NSCLC and completed all planned (eg, 4 to 6 cycles) platinum-based chemotherapy with at least 2 cycles in combination with pembrolizumab; must not have had progressive disease on tumor staging imaging scans following completion of all planned platinum chemotherapy
- •Are eligible for maintenance therapy with pembrolizumab ± pemetrexed in accordance with the package insert
- •Have tumor PD-L1 ≥1%
- •The last dose of platinum-based chemotherapy must be within 8 weeks of the first dose of the study drug in this study
- •Inclusion Criterion for All Cohorts
- •Subjects must also meet all of the following criteria to be eligible to participate in the study:
- •Have histologically confirmed NSCLC that is inoperable, locally advanced or metastatic (Stage IIIb/IV)
- •Have available at the site a representative formalin-fixed, paraffin-embedded tumor specimen that enabled diagnosis of NSCLC in a tissue block (preferred) or 10 unstained, serial slides, accompanied by an associated pathology report. Note: If the archival tissue is neither sufficient nor available, the subject may still be eligible, upon discussion with the Medical Monitor
- •Have provided written informed consent and any authorizations required by local law
- •Are ≥18 years of age
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Have NSCLC with epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations
- •Have gastrointestinal (GI) disease (eg, gastric or intestinal bypass surgery, pancreatic enzyme insufficiency, malabsorption syndrome, symptomatic inflammatory bowel disease, chronic diarrheal illness, and/or bowel obstruction) that may interfere with drug absorption or with interpretation of GI AEs
- •Have known symptomatic brain metastases requiring >10 mg/day of prednisone (or its equivalent). Subjects with previously diagnosed brain metastases are eligible if they have completed their treatment, have recovered from the acute effects of radiation therapy or surgery prior to randomization, fulfill the steroid requirement for these metastases, the 2 most recent serial magnetic resonance imaging (MRI) scans conducted >28 days apart show no central nervous system progression, and are neurologically stable and asymptomatic
研究组 & 干预措施
A1 Tomi + Current Pembro
Subjects who have initiated pembrolizumab as a single agent and in accordance with the package insert will receive tomivosertib in addition to pembrolizumab.
干预措施: Tomivosertib (Drug)
A1 Tomi + Current Pembro
Subjects who have initiated pembrolizumab as a single agent and in accordance with the package insert will receive tomivosertib in addition to pembrolizumab.
干预措施: Pembrolizumab (Biological)
Pbo + Current Pembro
Subjects who have initiated pembrolizumab as a single agent and in accordance with the package insert, will receive matching placebo in addition to pembrolizumab.
干预措施: Pembrolizumab (Biological)
B1 Tomi + Pembro
Subjects will initiate pembrolizumab as first-line therapy and receive tomivosertib.
干预措施: Tomivosertib (Drug)
B1 Tomi + Pembro
Subjects will initiate pembrolizumab as first-line therapy and receive tomivosertib.
干预措施: Pembrolizumab (Biological)
Pbo + Pembro
Subjects will initiate pembrolizumab as first-line therapy and receive matching placebo.
干预措施: Pembrolizumab (Biological)
C1 Tomi + Pembro + Pemetrexed (Non-sqamous) or Tomi + Pembro (Squamous)
Subjects who have completed 4 to 6 cycles of platinum-based chemotherapy doublet will receive tomi plus pembrolizumab and pemetrexed (non-squamous NSCLC) or tomi plus pembro as a single agent (squamous) in accordance with the package insert.
干预措施: Tomivosertib (Drug)
C1 Tomi + Pembro + Pemetrexed (Non-sqamous) or Tomi + Pembro (Squamous)
Subjects who have completed 4 to 6 cycles of platinum-based chemotherapy doublet will receive tomi plus pembrolizumab and pemetrexed (non-squamous NSCLC) or tomi plus pembro as a single agent (squamous) in accordance with the package insert.
干预措施: Pembrolizumab (Biological)
C1 Tomi + Pembro + Pemetrexed (Non-sqamous) or Tomi + Pembro (Squamous)
Subjects who have completed 4 to 6 cycles of platinum-based chemotherapy doublet will receive tomi plus pembrolizumab and pemetrexed (non-squamous NSCLC) or tomi plus pembro as a single agent (squamous) in accordance with the package insert.
干预措施: Pemetrexed (Drug)
Pbo + Pembro + Pemetrexed (Non-sqamous) or Pbo + Pembro (Squamous)
Subjects who have completed 4 to 6 cycles of platinum-based chemotherapy doublet will receive placebo plus pembrolizumab and pemetrexed (non-squamous NSCLC) or placebo plus pembro as a single agent (squamous) in accordance with the package insert.
干预措施: Pembrolizumab (Biological)
Pbo + Pembro + Pemetrexed (Non-sqamous) or Pbo + Pembro (Squamous)
Subjects who have completed 4 to 6 cycles of platinum-based chemotherapy doublet will receive placebo plus pembrolizumab and pemetrexed (non-squamous NSCLC) or placebo plus pembro as a single agent (squamous) in accordance with the package insert.
干预措施: Pemetrexed (Drug)
结局指标
主要结局
To characterize the PFS of tomivosertib when added to pembrolizumab and pemetrexed in non-squamous NSCLC, and pembrolizumab in squamous NSCLC as first line maintenance therapy.
时间窗: 2 years
Defined as the time from randomization to the first occurrence of disease progression as assessed by the Investigator using RECIST 1.1 or death from any cause, whichever occurs earlier.
To characterize the PFS of tomivosertib when added to pembrolizumab as first line therapy.
时间窗: 2 years
Defined as the time from randomization to the first occurrence of disease progression as assessed by the Investigator using RECIST 1.1 or death from any cause, whichever occurs earlier.
To characterize the progression-free survival (PFS) of tomivosertib when added to pembrolizumab as a first-line treatment; and
时间窗: 2 years
Defined as the time from randomization to the first occurrence of disease progression as assessed by the Investigator using RECIST 1.1 or death from any cause, whichever occurs earlier.
次要结局
- To characterize the PFS of tomivosertib when added to pembrolizumab in Cohorts A, B, and B C individually and combined(2 years)
- To characterize the PFS of tomivosertib when added to pembrolizumab and pemetrexed in non-squamous NSCLC, and pembrolizumab in squamous NSCLC as a first-line maintenance treatment in subjects with NSCLC.(2 years)
- To characterize the PFS of tomivosertib when added to pembrolizumab as a first-line treatment in subjects with NSCLC(2 years)
- To characterize the PFS of tomivosertib when added to pembrolizumab after first radiographic progression on pembrolizumab monotherapy(2 years)