Phase 2 Non-randomized, Open-label, Multi-cohort, Multicenter Study Assessing the Clinical Benefit of SAR444245 (THOR-707) With or Without Other Anticancer Therapies for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 14
- 试验地点
- 8
- 主要终点
- Complete Response Rate (CRR)
研究概览
简要总结
This is a phase 2 multi-cohort, un-controlled, non-randomized, open-label, multi-center study that assessed the antitumor activity and safety of non-alpha interleukin (IL-2) SAR444245 with or without other anticancer therapies in participants aged 12 years and older with relapsed or refractory B cell lymphoma. This study was structured as a master protocol with separate sub studies designed to investigate the use of SAR444245 either with or without other anticancer therapies for the treatment of relapsed or refractory B cell lymphoma.
Substudy 1-Cohort A aimed to establish safety and preliminary anti-tumor activity for non-alpha interleukin (IL-2) SAR444245 combined with the anti-PD1 antibody, pembrolizumab in trial participants with classic Hodgkin lymphoma (cHL) who are anti-PD-(L)1-naive and have received at least 2 or 3 lines of systemic therapy.
Substudy 3-Cohort C1 aims to establish safety and preliminary anti-tumor activity for SAR444245 as monotherapy in trial participants with diffuse large B-cell lymphoma (DLBCL). Trial participants in this study must have received at least 2 lines of systemic therapy and have either stable or progressive disease 1-3 months post Health Authority approved Chimeric Antigen Receptor T-cell (CAR-T) treatment when given as last systemic treatment prior to study enrollment.
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 (21 days per cycle) for Cohort A and 52 cycles (14 days per cycle) for Cohort C1 or until occurrence of unacceptable toxicities or until PD;
an end-of-treatment visit at least approximately 30 days following the last administration of study drug (or until the participant receives another anticancer therapy, whichever is earlier);
and a follow-up visits 3 months after treatment discontinuation and every 3 months thereafter 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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have been ≥ 12 years of age, at the time of signing the informed consent
- •Disease location was amenable to tumor biopsy at baseline
- •All participants must have had a measurable disease
- •Both male and female participants agreed to use approved contraception methods; not pregnant or breastfeeding for female participants; no donation or cryopreservation of eggs (ova, oocytes) for female participants and sperms for male participants.
- •Had to be capable of giving signed informed consent
- •For cohort A: Histologically or cytologically confirmed diagnosis of classic Hodgkin lymphoma (cHL), must have received at least two prior lines of systemic therapy for cHL, including at least one containing an anthracycline or brentuximab.
- •For cohort C1: Histologically confirmed diagnosis of diffuse large B Cell lymphoma (DLBCL), must have received at least two prior lines of systemic therapy for DLBCL, including one containing a combination of anthracycline and rituximab (or another anti-CD20 agent), with the last line of therapy a Health Authority approved CD19-directed CAR-T therapy. Patients must have BOR (Best Overall Response) of stable disease (SD) or progressive disease (PD) after CD-19 directed CAR-T therapy.
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 ≥ 2 (≥ 16 years old). Lansky Scale (< 16 years old) ≤ 60%
- •Poor bone marrow reserve
- •Poor organ function
- •Participants with baseline oxygen saturation (SpO2) ≤ 92% (without oxygen therapy)
- •Lymphomatous involvement of the central nervous system
- •History of allogenic or solid organ transplant
- •Prior IV or subcutaneous anticancer therapy, investigational agent, major surgery within 21 days prior to initiation of IMP; oral anticancer therapy within 5 half-lives or completed palliative radiotherapy within 21 days prior to initiation of IMP
- •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
- •Had 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
- •Receipt of a live or live attenuated virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines or SARS-CoV-2 vaccine that do not contain live virus were 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 A: Pegenzileukin 24 μg/kg + Pembrolizumab
Participants with classic Hodgkin lymphoma (cHL) who were anti-programmed cell death-ligand 1 (PD-L1)-naïve and had received at least 2 or 3 lines of systemic therapy received pegenzileukin 24 microgram per kilogram (μg/kg) via intravenous (IV) infusion over 30 minutes on Day 1 of each cycle (each cycle is 21 days), along with pembrolizumab 200 milligram (mg) via 30 minutes IV infusion on Day 1 of each 3-week treatment cycle (each cycle is 21 days) as third-line or fourth-line (3/4L) 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 A: Pegenzileukin 24 μg/kg + Pembrolizumab
Participants with classic Hodgkin lymphoma (cHL) who were anti-programmed cell death-ligand 1 (PD-L1)-naïve and had received at least 2 or 3 lines of systemic therapy received pegenzileukin 24 microgram per kilogram (μg/kg) via intravenous (IV) infusion over 30 minutes on Day 1 of each cycle (each cycle is 21 days), along with pembrolizumab 200 milligram (mg) via 30 minutes IV infusion on Day 1 of each 3-week treatment cycle (each cycle is 21 days) as third-line or fourth-line (3/4L) 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 C1: (sub study 03) diffuse large B Cell lymphoma (DLBCL)
Pegenzileukin administered every 2 weeks on Day 1 of each cycle (14 days per cycle) for up to 52 cycles.
干预措施: THOR-707 (Drug)
结局指标
主要结局
Complete Response Rate (CRR)
时间窗: From first dose of study treatment administration (Day 1) up to approximately 21 months
The CRR was defined as the percentage of participants who had a complete response (CR) as the best overall response (BOR) as per Investigator assessment (Lugano response criteria 2014). The BOR was defined as the BOR observed from the date of first study treatment until PD, death, cut-off date or initiation of subsequent anti-cancer therapy, whichever occurred first. CR based on computed tomography (CT)-based response: lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5 centimeter (cm) in longest transverse diameter of a lesion (LDi) and no extralymphatic sites of disease.
次要结局
- Objective Response Rate (ORR)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months)
- 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 29 months)
- Number of Participants With Dose Limiting Toxicities (DLTs)(From Day 1 to Day 21 of Cycle 1 (each cycle is 21 days))
- Time to Response (TTR)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months)
- Duration of Response (DoR)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months)
- Clinical Benefit Rate (CBR)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months)
- Progression Free Survival (PFS)(From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months)
- Plasma Concentrations of Pegenzileukin(Cycle 1 Day 2, Cycle 1 Day 3 (each cycle is 21 days))
- Concentration at End of Infusion (Ceoi) of Pegenzileukin(Cycles 1, 2, 4, 7, 10, 15 (each cycle is 21 days))
- Number of Participants With Anti-Drug Antibodies (ADA) Against Pegenzileukin(From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 29 months)