Study of [212Pb]Pb-DOTAM-MAM279 ([212Pb]Pb-MP0712) in Patients With Small Cell Lung Cancer and Other DLL3 Expressing Solid Tumors

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат [212Pb]Pb-MP0712
  Radioligand Therapy
• Другое [203Pb]Pb-MP0712
  Radioligand Imaging Agent

Первичные конечные точки

• To assess incidence and severity of safety events following administration of [212Pb]Pb-DOTAM-MAM279 [Срок оценки: until 5 years after last dose]
• To assess dose modifications of [212Pb]Pb-DOTAM-MAM279 [Срок оценки: until 5 years after last dose]
• 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 [Срок оценки: Phase 1, from start of treatment to end of first cycle (day 1 - 28)]
• To evaluate the preliminary anti-tumor activity of [212Pb]Pb-DOTAM-MAM279 in the dose expansion part [Срок оценки: Phase 2a only; 12 months]

Вторичные конечные точки (11)

• To assess maximum concentration (Cmax) of [203Pb]Pb-DOTAM-MAM279 / [212Pb]Pb-DOTAM-MAM279 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: up to 10 days following [203Pb]Pb-DOTAM-MAM279 administration]
• To evaluate PFS [Срок оценки: Phase 2a only; 12 months]
• To evaluate DoR [Срок оценки: Phase 2a only; 12 months]
• To evaluate DCR [Срок оценки: Phase 2a only; 12 months]
• To evaluate OS [Срок оценки: Phase 2a only; approx. 5 years]

Критерии участия

Критерии включения

• 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 v1.1.
• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 5 центров

• Emory University Hospital — Atlanta
• United Theranostics — Glen Burnie
• Nebraska Cancer Specialists — Omaha
• United Theranostics — Princeton
• University Hospitals Cleveland Medical Center — Cleveland

Идентификаторы

NCT: NCT07278479 · MP0712-CP101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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