A Phase 1/2a Study to Assess Safety, Tolerability, and Efficacy of [212Pb]Pb-DOTAM-MAM279 in Patients With Small Cell Lung Cancer and Other DLL3 Expressing Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 138
- 试验地点
- 5
- 主要终点
- To estimate the maximum tolerated dose (MTD) and/or to define the recommended phase 2 dose (RP2D) for SCLC/LCNEC of the lung and epNECs
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of [212Pb]Pb-MP0712, in patients aged ≥18 years with Small Cell Lung Cancer and other locally advanced or metastatic DLL3 positive tumors.
详细描述
This is a phase I/IIa, open-label, multi-center study to evaluate the safety, tolerability, dosimetry, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of [212Pb]Pb-MP0712 in patients with SCLC and other advanced DLL3-expressing solid tumors. The study consists of a dose escalation part, followed by a dose expansion part. Once the recommended radioactive dose(s) [212Pb]Pb-MP0712 for further clinical evaluation are determined, the dose expansion part will further characterize the safety, tolerability, and preliminary anti-tumor activity of [212Pb]Pb-MP0712. The study will enable evaluation of the safety, dosimetry, PK, and imaging properties of [203Pb]Pb-MP0712.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Age ≥ 18 years old
- •Histologically or cytologically confirmed: I. advanced extensive or limited SCLC or LC NECs of the lung
- •SCLC (extensive stage, or limited stage) patients with progression or recurrence following at least two prior line of systemic platinum based therapy and immunotherapy or are not suitable or tolerating the standard of care treatment as second line of systemic therapy, or
- •LC NEC of the lung patients with progression or recurrence following at least one prior line of systemic therapy, or II. epNECs with progression or recurrence following at least one prior line of systemic therapy:
- •Gastroenteropancreatic NECs (GEPNEC), or
- •Cervical NECs, or
- •Bladder NECs, or
- •other epNECs with previously confirmed DLL3 expression by IHC.
- •Patients with prior DLL3-targeted therapy are allowed.
- •For epNECs in Part 1 and Part 2 and SCLC or LC NECs of the lung in Part 2: DLL3-positivity by [203Pb]Pb-DOTAM-MAM279 SPECT/CT
- •Radiographically documented disease progression or recurrence during or after the last line of systemic treatment therapy
- •At least one measurable disease per RECIST v1.
- •Adequate bone marrow reserve and organ function as demonstrated by complete blood count, and biochemistry in blood and urine at Screening
- •Adequate blood counts: Hemoglobin ≥9 g/dL; Absolute neutrophil count (ANC) ≥1.5 × 10^9/L; Platelets ≥100 × 10^9/L; White blood cells (WBC) ≥2.5 x 10^9/L;
- •Adequate hepatic function
- •Adequate renal function: Calculated glomerular filtration rate (GFR) >60mL/min (using Cockroft-Gault formula).
- •Patients with known central nervous system (CNS) metastasis will be eligible if they are clinically stable.
排除标准
- •Uncontrolled intercurrent illness
- •Patients who have not had resolution of all clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade ≤1 (except for grade ≤2 alopecia, or stable grade 2 sensory neuropathy, according to the last CTCAE version).
- •Active clinically significant cardiac disease
- •Evidence of interstitial lung disease or active, non-infectious pneumonitis.
- •History of other malignancy within the past 2 years with exceptions.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
[203Pb]Pb-DOTAM-MAM279/[212Pb]Pb-DOTAM-MAM279
Patients will receive [203Pb]Pb-DOTAM-MAM279 for Imaging/Dosimetry followed by [212Pb]Pb-DOTAM-MAM279 for treatment
干预措施: [203Pb]Pb-MP0712 (Other)
[203Pb]Pb-DOTAM-MAM279/[212Pb]Pb-DOTAM-MAM279
Patients will receive [203Pb]Pb-DOTAM-MAM279 for Imaging/Dosimetry followed by [212Pb]Pb-DOTAM-MAM279 for treatment
干预措施: [212Pb]Pb-MP0712 (Drug)
结局指标
主要结局
To estimate the maximum tolerated dose (MTD) and/or to define the recommended phase 2 dose (RP2D) for SCLC/LCNEC of the lung and epNECs
时间窗: Phase 1, from start of treatment to end of first cycle (day 1 - 28)
Incidence of dose limiting toxicities
To evaluate the preliminary anti-tumor activity of [212Pb]Pb-DOTAM-MAM279 in the dose expansion part
时间窗: Phase 2a only; 12 months
Objective Response Rate (ORR) in the expansion phase ORR is defined as the percentage of patients with partial response (PR) or complete response (CR) as per RECIST v1.1
To assess incidence and severity of safety events following administration of [212Pb]Pb-DOTAM-MAM279
时间窗: until 5 years after last dose
Type, frequency and severity of adverse events (AEs), and serious adverse events (SAEs), Adverse events of special interest (AESI) and Dose Limiting Toxicities (DLT) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
To assess dose modifications of [212Pb]Pb-DOTAM-MAM279
时间窗: until 5 years after last dose
Frequency and duration of dose changes
To estimate the maximum tolerated dose (MTD) and/or to define the recommended phase 2 dose (RP2D) for SCLC/LCNEC of the lung and epNECs
时间窗: Phase 1, from start of treatment to end of first cycle (day 1 - 28)
Incidence of dose limiting toxicities
To evaluate the preliminary anti-tumor activity of [212Pb]Pb-DOTAM-MAM279 in the dose expansion part
时间窗: Phase 2a only; 12 months
Objective Response Rate (ORR) in the expansion phase ORR is defined as the percentage of patients with partial response (PR) or complete response (CR) as per RECIST v1.1
次要结局
- To assess maximum concentration (Cmax) of [203Pb]Pb-DOTAM-MAM279 / [212Pb]Pb-DOTAM-MAM279(up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration; up to 14 days following [212Pb]Pb-DOTAM-MAM279 administration])
- To assess the area under the curve (AUC) from time 0 to the time of the last quantifiable concentration of [203Pb]Pb-DOTAM-MAM279(up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration; up to 14 days following [212Pb]Pb-DOTAM-MAM279 administration])
- To assess half-live(s) (t½) of [203Pb]Pb-DOTAM-MAM279 / [212Pb]Pb-DOTAM-MAM279(up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration; up to 14 days following [212Pb]Pb-DOTAM-MAM279 administration])
- To assess the clearance (CL) of [203Pb]Pb-DOTAM-MAM279 / [212Pb]Pb-DOTAM-MAM279(up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration; up to 14 days following [212Pb]Pb-DOTAM-MAM279 administration])
- To assess the volume of distribution (Vd) of [203Pb]Pb-DOTAM-MAM279 / [212Pb]Pb-DOTAM-MAM279(up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration; up to 14 days following [212Pb]Pb-DOTAM-MAM279 administration])
- To quantitatively predict radiation absorbed doses for therapeutic [212Pb]Pb-DOTAM-MAM279 from [203Pb]Pb-DOTAM-MAM279(Phase 1; up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration)
- To assess incidence and severity of safety events following administration of [203Pb]Pb-DOTAM-MAM279(up to 10 days following [203Pb]Pb-DOTAM-MAM279 administration)
- To evaluate PFS(Phase 2a only; 12 months)
- To evaluate DoR(Phase 2a only; 12 months)
- To evaluate DCR(Phase 2a only; 12 months)
- To assess the volume of distribution (Vd) of [203Pb]Pb-DOTAM-MAM279 / [212Pb]Pb-DOTAM-MAM279(up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration; up to 14 days following [212Pb]Pb-DOTAM-MAM279 administration])
- To evaluate DCR(Phase 2a only; 12 months)
- To assess maximum concentration (Cmax) of [203Pb]Pb-DOTAM-MAM279 / [212Pb]Pb-DOTAM-MAM279(up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration; up to 14 days following [212Pb]Pb-DOTAM-MAM279 administration])
- To assess the clearance (CL) of [203Pb]Pb-DOTAM-MAM279 / [212Pb]Pb-DOTAM-MAM279(up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration; up to 14 days following [212Pb]Pb-DOTAM-MAM279 administration])
- To evaluate PFS(Phase 2a only; 12 months)
- To evaluate DoR(Phase 2a only; 12 months)
- To assess the area under the curve (AUC) from time 0 to the time of the last quantifiable concentration of [203Pb]Pb-DOTAM-MAM279(up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration; up to 14 days following [212Pb]Pb-DOTAM-MAM279 administration])
- To assess half-live(s) (t½) of [203Pb]Pb-DOTAM-MAM279 / [212Pb]Pb-DOTAM-MAM279(up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration; up to 14 days following [212Pb]Pb-DOTAM-MAM279 administration])
- To quantitatively predict radiation absorbed doses for therapeutic [212Pb]Pb-DOTAM-MAM279 from [203Pb]Pb-DOTAM-MAM279(Phase 1; up to 7 days following [203Pb]Pb-DOTAM-MAM279 administration)
- To assess incidence and severity of safety events following administration of [203Pb]Pb-DOTAM-MAM279(up to 10 days following [203Pb]Pb-DOTAM-MAM279 administration)
- To evaluate OS(Phase 2a only; approx. 5 years)