Phase 1b/2a Safety and Tolerability Study of Bemcentinib With Pembrolizumab/Carboplatin/Pemetrexed in Subjects With Untreated Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Without/With a STK11 Mutation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 34
- 主要终点
- Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)
研究概览
简要总结
The primary purpose of this study is to determine the safety and tolerability of the combination of bemcentinib with chemo-immunotherapy (CIT) to identify the recommended phase 2 dose (RP2D) when administered as first line (1L) treatment in participants with locally advanced (Stage IIIb/IIIC) or metastatic (Stage IV) non-squamous NSCLC with no actionable mutations and to determine the anti-tumor activity of the combination of bemcentinib with CIT when administered as 1L treatment in participants with locally advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC with serine/threonine kinase 11 (STK11) mutation and no actionable mutations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Histologically-confirmed or cytologically confirmed diagnosis of advanced (Stage IIIb/IIIc) or metastatic (Stage IV) (AJCC Edition 8) non-squamous NSCLC not amenable to curative therapy, irrespective of PD-L1 status and without actionable mutations (Phase 1b) targetable with first-line treatment.
- •Histologically-confirmed or cytologically confirmed diagnosis of stage of advanced (Stage IIIb/IIIC) or metastatic (Stage IV) (AJCC, Edition 8) non-squamous NSCLC with STK11 mutation, not amenable to curative therapy, irrespective of PD-L1 status and without actionable mutations (phase 2a) targetable with first-line treatment.
- •Have not received prior systemic treatment for their advanced/metastatic NSCLC
- •Have measurable disease per RECIST 1.1 as assessed by the investigator
排除标准
- •Has received any prior chemotherapy or biological therapy for locally advanced (Stage IIIb/IIIc) or metastatic (Stage IV) adenocarcinoma of the lung
- •Received radiation therapy within 2 weeks prior to starting study treatment or has not recovered (i.e. <=Grade 1 at baseline) from AEs due to a previous radiation therapy
- •Major surgery within 28 days prior to start of study treatment and failure to have recovered adequately from the complications of the surgery/intervention prior to the first dose of study treatment
研究组 & 干预措施
Phase 1b Cohort 1: Bemcentinib 75 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 75 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Bemcentinib (Drug)
Phase 1b Cohort 1: Bemcentinib 75 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 75 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Pembrolizumab (Drug)
Phase 1b Cohort 1: Bemcentinib 75 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 75 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Pemetrexed (Drug)
Phase 1b Cohort 1: Bemcentinib 75 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 75 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Carboplatin (Drug)
Phase 1b Cohort 2: Bemcentinib 100 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 100 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Bemcentinib (Drug)
Phase 1b Cohort 2: Bemcentinib 100 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 100 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Pembrolizumab (Drug)
Phase 1b Cohort 2: Bemcentinib 100 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 100 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Pemetrexed (Drug)
Phase 1b Cohort 2: Bemcentinib 100 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 100 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Carboplatin (Drug)
Phase 1b Cohort 3: Bemcentinib 150 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 150 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Bemcentinib (Drug)
Phase 1b Cohort 3: Bemcentinib 150 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 150 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Pembrolizumab (Drug)
Phase 1b Cohort 3: Bemcentinib 150 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 150 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Pemetrexed (Drug)
Phase 1b Cohort 3: Bemcentinib 150 mg
Participants with previously untreated locally advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC without actionable mutations will receive bemcentinib 150 mg once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Carboplatin (Drug)
Phase 2a Expansion Cohort: Bemcentinib 100 mg (as the dose determined from Phase 1b)
Participants with previously untreated advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC having a serine/threonine kinase 11 (STK11) mutation as identified by Next Generation Sequencing (NGS) and without actionable mutations will receive bemcentinib second dose, at RP2D identified in Phase 1b, once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Bemcentinib (Drug)
Phase 2a Expansion Cohort: Bemcentinib 100 mg (as the dose determined from Phase 1b)
Participants with previously untreated advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC having a serine/threonine kinase 11 (STK11) mutation as identified by Next Generation Sequencing (NGS) and without actionable mutations will receive bemcentinib second dose, at RP2D identified in Phase 1b, once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Pembrolizumab (Drug)
Phase 2a Expansion Cohort: Bemcentinib 100 mg (as the dose determined from Phase 1b)
Participants with previously untreated advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC having a serine/threonine kinase 11 (STK11) mutation as identified by Next Generation Sequencing (NGS) and without actionable mutations will receive bemcentinib second dose, at RP2D identified in Phase 1b, once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Pemetrexed (Drug)
Phase 2a Expansion Cohort: Bemcentinib 100 mg (as the dose determined from Phase 1b)
Participants with previously untreated advanced (Stage IIIb/IIIc)/metastatic (Stage IV) non-squamous NSCLC having a serine/threonine kinase 11 (STK11) mutation as identified by Next Generation Sequencing (NGS) and without actionable mutations will receive bemcentinib second dose, at RP2D identified in Phase 1b, once daily until a reason for discontinuation has been met or for up to 2 years, whichever occurs first along with CIT (pembrolizumab infusion followed by pemetrexed and carboplatin).
干预措施: Carboplatin (Drug)
结局指标
主要结局
Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)
时间窗: Cycle 1 (the first 21 days of treatment)
DLT graded using NCI CTCAE Version 5.0 based on the Investigator assessment.
Phase 2a: Objective Response Rate (ORR) at 6 Months
时间窗: 6 months
ORR is defined as percentage of participants with complete response and partial response per RECIST 1.1.
Phase 2a: Objective Response Rate (ORR) at 12 Months
时间窗: 12 months
ORR is defined as percentage of participants with complete response and partial response per RECIST 1.1.
次要结局
未报告次要终点