A Phase 2 Non-randomized, Open-label, Multi-cohort, Multi-center Study Assessing the Clinical Benefit of SAR444245 (THOR-707) Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Pleural Mesothelioma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 106
- 试验地点
- 35
- 主要终点
- Cohorts A1 and A2: Objective Response Rate (ORR)
研究概览
简要总结
The Primary Objective was:
-To determine the antitumor activity of SAR444245 in combination with other anticancer therapies.
The Secondary Objectives were:
- To confirm the dose and to assess the safety profile of SAR444245 when combined with other anticancer therapies.
- To assess other indicators of antitumor activity.
- To assess the pharmacokinetic (PK) profile of SAR444245 when given in combination with pembrolizumab.
- To assess the immunogenicity of SAR444245.
详细描述
The duration of the study for an individual participant started from the signature of the main informed consent and included a screening period of up to 28 days, a treatment period [max 35 cycles {cohorts A1, A2, and B1} = 735 days or until PD {cohort C1}], an end-of-treatment visit at least 30 days following the last administration of study drug (or until the participant receives another anticancer therapy, whichever is earlier), and a follow-up visit 3 months after treatment discontinuation and every 3 months following, until disease progression, or initiation of another antitumor treatment, or death, whichever is earlier
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Participant must have been ≥18 years of age (or country's legal age of majority if >18 years), at the time of signing the informed consent.
- •Histologically or cytologically confirmed diagnosis of Stage IV NSCLC (cohorts A1, A2, and B1), or unresectable malignant pleural mesothelioma (cohort C1).
- •Cohort A1: PD-L1 expression TPS ≥ 50%
- •Cohort A2: PD-L1 expression TPS 1 - 49%
- •Prior anticancer therapy
- •Cohorts A1 and A2: No prior systemic therapy for advanced/metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the development of metastatic disease.
- •Cohort B1: One prior anti-PD1/PD-L1 regimen (may include chemotherapy) plus one additional chemotherapy regimen
- •Cohort C1: One or two prior systemic treatments that include pemetrexed-based regimen in combination with platinum agent.
- •All cohorts must have had a measurable disease
- •Mandatory baseline biopsy for the first 20 participants to enroll in cohorts A1, A2
- •Cohort B1: Based on the Investigator's judgment, either docetaxel or pemetrexed is not the best treatment option for the participant.
- •Females were eligible to participate if they were not pregnant or breastfeeding, not a woman of childbearing potential (WOCBP) or are a WOCBP that agrees:
- •to use approved contraception method and submit to regular pregnancy testing prior to treatment and for 150 days after discontinuing study treatment
- •to refrain from donating or cryopreserving eggs for 150 days after discontinuing study treatment.
- •Males were eligible to participate if they agree to refrain from donating or cryopreserving sperm, and either abstain from heterosexual intercourse OR use approved contraception during study treatment and for at least 210 days after discontinuing study treatment.
- •Capable of giving signed informed consent.
排除标准
- •Participants were excluded from the study if any of the following criteria applied:
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≥
- •Poor bone marrow reserve
- •Poor organ function
- •Participants with baseline SpO2 ≤ 92%.
- •Active brain metastases or leptomeningeal disease.
- •History of allogenic tissue/solid organ transplant
- •Last administration of prior antitumor therapy or any investigational treatment within 28 days or less than 5 times the half-life, whichever is shorter; major surgery or local intervention within 28 days.
- •Has received prior IL-2-based anticancer treatment.
- •Comorbidity requiring corticosteroid therapy
- •Antibiotic use (excluding topical antibiotics) ≤14 days prior to first dose of IMP
- •Severe or unstable cardiac condition within 6 months prior to starting study treatment
- •Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years
- •Known second malignancy either progressing or requiring active treatment within the last 3 years
- •Cohorts A1, A2, and C1: Prior treatment with an agent (approved or investigational) that blocks the PD1/PD-L1 pathway (participants who joined a study with an anti-PD1/PD-L1 but have written confirmation they were on control arm are allowed).
- •Receipt of a live-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
- •The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
研究组 & 干预措施
Cohort A1: NSCLC, PD-L1 TPS >=50%:Pegenzileukin 24 μg/kg + Pembrolizumab as 1L Therapy
Participants with previously untreated Stage IV non-small cell lung cancer (NSCLC) and programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) of >=50% were included in this cohort. Participants received pegenzileukin 24 microgram per kilogram (μg/kg) along with pembrolizumab 200 milligram (mg) via intravenous (IV) infusion over 30 minutes every 3 weeks (q3w) on Day 1 of each cycle (each cycle is 21 days) (as first-line [1L] therapy), until disease progression (PD), unacceptable adverse event (AE) or other full permanent discontinuation criteria was met or completion of Cycle 35.
干预措施: THOR-707 (Drug)
Cohort A1: NSCLC, PD-L1 TPS >=50%:Pegenzileukin 24 μg/kg + Pembrolizumab as 1L Therapy
Participants with previously untreated Stage IV non-small cell lung cancer (NSCLC) and programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) of >=50% were included in this cohort. Participants received pegenzileukin 24 microgram per kilogram (μg/kg) along with pembrolizumab 200 milligram (mg) via intravenous (IV) infusion over 30 minutes every 3 weeks (q3w) on Day 1 of each cycle (each cycle is 21 days) (as first-line [1L] therapy), until disease progression (PD), unacceptable adverse event (AE) or other full permanent discontinuation criteria was met or completion of Cycle 35.
干预措施: Pembrolizumab (Drug)
Cohort A2: NSCLC, PD-L1 TPS 1%-49%:Pegenzileukin 24 μg/kg+Pembrolizumab as 1L Therapy
Participants with previously untreated Stage IV NSCLC and PD-L1 TPS of 1%-49% were included in this cohort. Participants received pegenzileukin 24 μg/kg along with pembrolizumab 200 mg via IV infusion over 30 minutes q3w on Day 1 of each cycle (each cycle is 21 days) (as 1L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.
干预措施: THOR-707 (Drug)
Cohort A2: NSCLC, PD-L1 TPS 1%-49%:Pegenzileukin 24 μg/kg+Pembrolizumab as 1L Therapy
Participants with previously untreated Stage IV NSCLC and PD-L1 TPS of 1%-49% were included in this cohort. Participants received pegenzileukin 24 μg/kg along with pembrolizumab 200 mg via IV infusion over 30 minutes q3w on Day 1 of each cycle (each cycle is 21 days) (as 1L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.
干预措施: Pembrolizumab (Drug)
Cohort B1: NSCLC:Pegenzileukin 24 μg/kg+Pembrolizumab as 2/3L Therapy
Participants with NSCLC for whom standard of care (SOC) was not in their best interest or where no SOC was established were included in this cohort. Participants received pegenzileukin 24 μg/kg along with pembrolizumab 200 mg via IV infusion over 30 minutes q3w on Day 1 of each cycle (each cycle is 21 days) (as second-line or third-line [2/3L] therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.
干预措施: THOR-707 (Drug)
Cohort B1: NSCLC:Pegenzileukin 24 μg/kg+Pembrolizumab as 2/3L Therapy
Participants with NSCLC for whom standard of care (SOC) was not in their best interest or where no SOC was established were included in this cohort. Participants received pegenzileukin 24 μg/kg along with pembrolizumab 200 mg via IV infusion over 30 minutes q3w on Day 1 of each cycle (each cycle is 21 days) (as second-line or third-line [2/3L] therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.
干预措施: Pembrolizumab (Drug)
Cohort C1: Mesothelioma: Pegenzileukin 24 μg /kg+Pembrolizumab as 2/3L Therapy
Participants with mesothelioma who had no SOC established and had experienced PD during or after at least one but no more than 2 prior regimens were included in this cohort. Participants received pegenzileukin 24 μg/kg along with pembrolizumab 200 mg via IV infusion over 30 minutes q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.
干预措施: THOR-707 (Drug)
Cohort C1: Mesothelioma: Pegenzileukin 24 μg /kg+Pembrolizumab as 2/3L Therapy
Participants with mesothelioma who had no SOC established and had experienced PD during or after at least one but no more than 2 prior regimens were included in this cohort. Participants received pegenzileukin 24 μg/kg along with pembrolizumab 200 mg via IV infusion over 30 minutes q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Cohorts A1 and A2: Objective Response Rate (ORR)
时间窗: From first dose of study treatment administration (Day 1) up to approximately 21 months
ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 millimeter (mm) (\<1 centimeter \[cm\]). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Cohorts B1: Objective Response Rate
时间窗: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 14 months
ORR was defined as the percentage of participants who had a confirmed CR or PR as per RECIST v1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Cohorts C1: Objective Response Rate
时间窗: From first dose of study treatment administration (Day 1) up to approximately 21 months
ORR was defined as the percentage of participants who had a confirmed CR or PR assessed by the investigator as per modified RECIST (mRECIST) v1.1. CR. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 28 months (Cohorts A1 and A2), 15 months (Cohort B1), and 25 months (Cohort C1))
- All Cohorts: Number of Participants With Dose Limiting Toxicities (DLTs)(From Day 1 to Day 21 of Cycle 1 (each cycle is 21 days))
- All Cohorts: Time to Response (TTR)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohorts A1 and A2), 14 months (Cohort B1), and 24 months (Cohort C1))
- All Cohorts: Duration of Response (DOR)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohorts A1 and A2), 14 months (Cohort B1), and 24 months (Cohort C1))
- All Cohorts: Clinical Benefit Rate (CBR)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohorts A1 and A2), 14 months (Cohort B1), and 24 months (Cohort C1))
- All Cohorts: Progression Free Survival (PFS)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohorts A1 and A2), 14 months (Cohort B1), and 24 months (Cohort C1))
- All Cohorts: Plasma Concentrations of Pegenzileukin(Days 2 and 3 of Cycle 1 (each cycle is 21 days))
- All Cohorts: Concentration at End of Infusion (Ceoi) of Pegenzileukin(Cycles 1, 2, 4, 7, 10, and 15 (each cycle is 21 days))
- All Cohorts: Number of Participants With Anti-Drug Antibodies (ADAs) Against Pegenzileukin(From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 28 months (Cohorts A1 and A2), 15 months (Cohort B1), and 25 months (Cohort C1))