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

NCT07278479 | Recruiting Phase 1 FDA Drug

• 1 other identifier: MP0712-CP101
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Extrapulmonary Neuroendocrine Carcinoma (EP-NEC); NEC of the Bladder; Large Cell Neuroendocrine Carcinoma; Large Cell Pulmonary Neuroendocrine Carcinoma of the Lung (LCNEC); Small Cell Lung Cancer (SCLC); Gastroenteropancreatic NEC (GEP NEC); Other DLL3 Expressing epNEC

Keywords

DARPin; Alpha Emitter; Pb203; Pb212; DLL3; Radioligand therapy (RLT); SCLC; Neuroendocrine cancer; [203Pb]Pb-DOTAM-MAM279; [212Pb]Pb-DOTAM-MAM279; EP-NEC; Lead 212; Lead 203; 203Pb; 212Pb

Outcome Measures

Primary Outcomes (4)

• 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)

  until 5 years after last dose

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

  Frequency and duration of dose changes

  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

  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

  Phase 2a only; 12 months

Secondary Outcomes (11)

• 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]

Study Arms (1)

[203Pb]Pb-DOTAM-MAM279/[212Pb]Pb-DOTAM-MAM279

EXPERIMENTAL

Patients will receive \[203Pb\]Pb-DOTAM-MAM279 for Imaging/Dosimetry followed by \[212Pb\]Pb-DOTAM-MAM279 for treatment

Drug: [212Pb]Pb-MP0712; Other: [203Pb]Pb-MP0712

Interventions

[212Pb]Pb-MP0712 DRUG

Radioligand Therapy

Also known as: [212Pb]Pb-DOTAM-MAM279

[203Pb]Pb-DOTAM-MAM279/[212Pb]Pb-DOTAM-MAM279

[203Pb]Pb-MP0712 OTHER

Radioligand Imaging Agent

Also known as: [203Pb]Pb-DOTAM-MAM279

[203Pb]Pb-DOTAM-MAM279/[212Pb]Pb-DOTAM-MAM279

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Molecular Partners AG: lead
• Orano Med LLC: collaborator

Study Sites (3)

United Theranostics

Glen Burnie, Maryland, 21061, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

United Theranostics

Princeton, New Jersey, 08540, United States

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Carcinoma, Neuroendocrine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Medical Director MPAG

CONTACT

+41 44 755 77 00; info@molecularpartners.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a phase 1/2a, multicenter, open-label study evaluating the safety, tolerability, and preliminary efficacy of \[212Pb\]Pb-DOTAM-MAM279 in patients with: * SCLC or LC NECs of the lung * epNECs The study is divided into two parts: * Part 1 (Phase 1): Dose escalation * Part 2 (Phase 2a): Dose expansion

Study Record Dates

• First Submitted: November 10, 2025
• First Posted: December 12, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2032
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

US (3)