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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Large Cell Neuroendocrine Carcinoma; Small Cell Lung Cancer (SCLC); Extrapulmonary Neuroendocrine Carcinoma (EP-NEC); Large Cell Pulmonary Neuroendocrine Carcinoma of the Lung (LCNEC); Gastroenteropancreatic NEC (GEP NEC); NEC of the Bladder; Other DLL3 Expressing epNEC
• Intervention / Treatment: Drug: [212Pb]Pb-MP0712; Other: [203Pb]Pb-MP0712

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 138
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Medical Director MPAG; Phone Number: +41 44 755 77 00; Email: info@molecularpartners.com

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital
      • Contact: Ryan Hanula; Phone Number: 404-778-5141; Email: rhanula@emory.edu
  • Maryland
    • Glen Burnie, Maryland, United States, 21061
      • Recruiting
      • United Theranostics
      • Contact: Amanda Huggins; Phone Number: 667-HOPENOW; Email: clinicaltrial@unithera.com
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Nebraska Cancer Specialists
      • Contact: Research Director; Phone Number: 402-955-2691; Email: clinicaltrials@nebraskacancer.com
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Recruiting
      • United Theranostics
      • Contact: Amanda Huggins; Phone Number: 667-HOPENOW; Email: clinicaltrial@unithera.com
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center
      • Contact: Dr A.Dowlati; Phone Number: 216-368-1122; Email: afshin.dowlati@uhhospitals.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [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	Drug: [212Pb]Pb-MP0712; Radioligand Therapy; Other Names: [212Pb]Pb-DOTAM-MAM279; Other: [203Pb]Pb-MP0712; Radioligand Imaging Agent; Other Names: [203Pb]Pb-DOTAM-MAM279

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	Blood and serum samples will be drawn to determine AUC 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 half-live(s) (t½) of [203Pb]Pb-DOTAM-MAM279 / [212Pb]Pb-DOTAM-MAM279	Blood and serum samples will be drawn to determine 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	Blood and serum samples will be drawn to determine 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	Blood and serum samples will be drawn to determine 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	Estimation of [212Pb]Pb-DOTAM-MAM279 absorbed dose for healthy organs and tumor lesions based on dosimetry analysis of [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	Type, frequency and severity of adverse events (AEs) and serious adverse events (SAEs) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0	up to 10 days following [203Pb]Pb-DOTAM-MAM279 administration
To evaluate PFS	Progression-Free Survival (PFS) determined as the time from C1D1 to the date of progression, defined as the first documented progression as per RECIST v1.1 or death for any cause	Phase 2a only; 12 months
To evaluate DoR	Duration of response (DoR) in patients with a CR or PR from date of first date of response to the date of RECIST 1.1 progression or death	Phase 2a only; 12 months
To evaluate DCR	Disease control rate (DCR) defined as the percentage of patients who have achieved CR, PR, or stable disease (SD)	Phase 2a only; 12 months
To evaluate OS	Overall survival (OS) defined as the time from C1D1 to death from any cause	Phase 2a only; approx. 5 years

Collaborators and Investigators

• Sponsor: Molecular Partners AG
• Collaborators: Orano Med LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2032

Study Registration Dates

• First Submitted: November 10, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Actual): December 12, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: SCLC; Lead 203; Lead 212; DLL3; DARPin; Neuroendocrine cancer; 212Pb; EP-NEC; Radioligand therapy (RLT); Alpha Emitter; Pb203; Pb212; [203Pb]Pb-DOTAM-MAM279; [212Pb]Pb-DOTAM-MAM279; 203Pb
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Small Cell Lung Carcinoma; Carcinoma, Neuroendocrine
• Other Study ID Numbers: MP0712-CP101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No