A First in Human Phase 1-2 Open-Label, Multicenter, Dose Escalation and Expansion Study of PRS-344/S095012 in Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 46
- 试验地点
- 15
- 主要终点
- Safety measurements
研究概览
简要总结
This is a first-in-human (FIH), phase 1/2, multi center, open-label, dose escalation and cohort expansion study designed to determine the safety and tolerability of PRS-344/S095012 in patients with advanced and/or metastatic solid tumors.
详细描述
The trial is an open-label, multi-center safety trial of PRS-344/S095012. The trial consists of two parts, a dose escalation part (phase 1, first-in-human (FIH) and an expansion part (phase 2)). The expansion part of the trial will be initiated once the optimal biological dose (OBD) has been determined. The study was terminated during phase 1 and thus, recruitment into phase 2 was not started.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Age ≥18 years on the day the consent is signed.
- •Patients with histologically confirmed diagnosis of unresectable, locally advanced or metastatic solid tumor for which standard treatment options are not available, no longer effective, or not tolerated.
- •Patient should have a documented disease progression on prior therapy before entry into this study.
- •Patients must have at least one measurable target lesion as per RECIST 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Patient with no available archived material must have one or more tumor lesions amenable to biopsy.
- •Adequate organ function as assessed by laboratory tests within 7 days prior to pretreatment with obinutuzumab.
- •A female patient must use a highly effective method of birth control during study treatment and for 120 days after last dose of PRS-344/S095012, or 18 months after the last obinutuzumab infusion, whichever comes the latest.
排除标准
- •Patients with previously treated brain metastases may participate provided they are radiologically stable, clinically asymptomatic and are off immunosuppressive therapies for at least 4 weeks. Low dose of steroid <10 mg/day prednisone or equivalent) is allowed.
- •Patients who have received prior:
- •Small molecule inhibitors, and/or other similar investigational agent: ≤ 2 weeks or 5 half-lives, whichever is shorter.
- •Chemotherapy, other monoclonal antibodies, antibody-drug conjugates, or other similar experimental therapies: ≤3 weeks or 5 half-lives, whichever is shorter.
- •Radioimmunoconjugates or other similar experimental therapies ≤6 weeks or 5 half-lives, whichever is shorter.
- •Patients who have received 4-1BB agonists in the past.
- •Patients who had a major surgery within 4 weeks prior to first administration of IMP.
- •History of progressive multifocal leukoencephalopathy.
- •Active tuberculosis requiring treatment within 3 years prior to the start of treatment or a suspicion of latent tuberculosis by the investigator.
研究组 & 干预措施
PRS-344/S095012
PRS-344/S095012
干预措施: PRS-344/S095012 (Drug)
结局指标
主要结局
Safety measurements
时间窗: 28 days
Phase 1: Incidence of dose-limiting toxicities (DLTs) over the first 28-days of study treatment
Safety Measurements
时间窗: time on trial, average of 6 months
Phase 1: Discontinuation of study treatment due to an AE
Objective Response (OR)
时间窗: Through study completion up to 24 months
Phase 2: Defined as Complete Response (CR) plus Partial Response (PR). For arms 1 and 2, per central assessment according to RECIST v1.1 criteria. For Arm 3, per central assessment and composite response criteria (digital medical photography and/or imaging as per RECIST v1.1)
Safety Measurements: Number of Participants With at Least One DLT in the First 28-days of Treatment
时间窗: 28 days
Phase 1: Dose-limiting toxicities (DLTs) over the first 28-days of study treatment
Safety Measurements: Number of Participants With at Least One AE
时间窗: Through study termination, approximately 3.5 years
Phase 1: Adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Safety Measurements: Number of Participants With at Least One AE Leading to Treatment Discontinuation
时间窗: Through study termination, approximately 3.5 years
Phase 1: Discontinuation of study treatment due to an AE
次要结局
- Mean PRS-344/S095012 concentrations at the end of the infusion(Through study completion up to 24 months)
- Mean PRS-344/S095012 trough concentrations (Ctrough)(Through study completion up to 24 months)
- Detection of anti-drug antibodies (ADA) against PRS-344/S095012(Through study completion up to 24 months)
- Objective Response (OR)(Through study completion up to 24 months)
- Duration of Response (DoR)(Through study completion up to 24 months)
- Progression-free Survival (PFS)(Through study completion up to 24 months)
- Overall Survival (OS)(Through study completion up to 24 months)
- Disease Control (DC)(Through study completion up to 24 months)
- Time to Response (TTR)(Through study completion up to 24 months)
- Serum concentrations of PRS-344/S095012(Through study completion up to 24 months)
- Safety measurements(time on trial, average of 6 months)
- Mean PRS-344/S095012 Concentrations at the End of the Infusion(Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle was 28 days))
- Mean PRS-344/S095012 Trough Concentrations (Ctrough)(Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 3 Day 15, Cycle 4 Day 1, Cycle 4 Day 15, Cycle 5 Day 1, Cycle 5 Day 15, Cycle 6 Day 1 (each cycle was up to 28 days))
- Number of Participants With at Least One Positive Anti-drug Antibody (ADA) Titer Result PRS-344/S095012(Through study termination, approximately 3.5 years)
- Objective Response Rate (ORR)(Through study termination, approximately 3.5 years)
- Best Overall Response (BOR)(Through study termination, approximately 3.5 years)
- Best Tumor Shrinkage From Baseline(Through study termination, approximately 3.5 years)