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

Phase 2RecruitingNCT07278479

Molecular Partners AG138 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

138

Conditions

Large Cell Neuroendocrine Carcinoma Large Cell Pulmonary Neuroendocrine Carcinoma of the Lung (LCNEC)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * 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. Key Exclusion Criteria: * 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.

Outcomes

Primary Outcomes

To assess incidence and severity of safety events following administration of [212Pb]Pb-DOTAM-MAM279

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)

Time frame: until 5 years after last dose

To assess dose modifications of [212Pb]Pb-DOTAM-MAM279

Frequency and duration of dose changes

Time frame: 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

Incidence of dose limiting toxicities

Time frame: 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

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

Time frame: Phase 2a only; 12 months

Secondary Outcomes

To assess maximum concentration (Cmax) of [203Pb]Pb-DOTAM-MAM279 / [212Pb]Pb-DOTAM-MAM279

Blood and serum samples will be drawn to determine maximum concentration (Cmax) of \[203Pb\]Pb-DOTAM-MAM279 / \[212Pb\]Pb-DOTAM-MAM279