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

Molecular Partners

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Large Cell Neuroendocrine Carcinoma

Extrapulmonary Neuroendocrine Carcinoma (EP-NEC)

Gastroenteropancreatic NEC (GEP NEC)

Small Cell Lung Cancer (SCLC)

NEC of the Bladder

Large Cell Pulmonary Neuroendocrine Carcinoma of the Lung (LCNEC)

Other DLL3 Expressing epNEC

Treatments

Drug: [212Pb]Pb-MP0712

Other: [203Pb]Pb-MP0712

Study type

Interventional

Funder types

Industry

Identifiers

NCT07278479

MP0712-CP101

Details and patient eligibility

About

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.

Full description

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.

Enrollment

138 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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.