Large Cell Neuroendocrine CarcinomaPhase 1/2NCT07278479
Study of [212Pb]Pb-DOTAM-MAM279 ([212Pb]Pb-MP0712) in Patients With Small Cell Lung Cancer and Other DLL3 Expressing Solid Tumors
A Phase 1/2 study testing [212Pb]Pb-MP0712 and [203Pb]Pb-MP0712 in people with Large Cell Neuroendocrine Carcinoma and Large Cell Pulmonary Neuroendocrine Carcinoma of the Lung (LCNEC), run by Molecular Partners AG at 8 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Large Cell Neuroendocrine Carcinoma, Large Cell Pulmonary Neuroendocrine Carcinoma of the Lung (LCNEC), Extrapulmonary Neuroendocrine Carcinoma (EP-NEC)
- What is being tested?
- [212Pb]Pb-MP0712 and [203Pb]Pb-MP0712
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- 8 sitesUnited States
- Study dates
- 18 May 2026to Sep 2032
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
United States8 sites, 8 recruiting
- Recruiting
Emory University Hospital
Atlanta, Georgia, 30322
Ryan Hanula, 404-778-5141, rhanula@emory.edu
- Recruiting
University of Chicago
Chicago, Illinois, 60637
- Recruiting
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Dr A.Dowlati, 216-368-1122, afshin.dowlati@uhhospitals.org
- Recruiting
United Theranostics
Glen Burnie, Maryland, 21061
Amanda Huggins, 667-HOPENOW, clinicaltrial@unithera.com
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Nebraska Cancer Specialists
Omaha, Nebraska, 68130
Research Director, 402-955-2691, clinicaltrials@nebraskacancer.com
- Recruiting
United Theranostics
Princeton, New Jersey, 08540
Amanda Huggins, 667-HOPENOW, clinicaltrial@unithera.com
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: 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.
Read the 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.
- Conditions
- Large Cell Neuroendocrine Carcinoma, Large Cell Pulmonary Neuroendocrine Carcinoma of the Lung (LCNEC), Extrapulmonary Neuroendocrine Carcinoma (EP-NEC), Small Cell Lung Cancer (SCLC), Gastroenteropancreatic NEC (GEP NEC), NEC of the Bladder
- Being tested
- [212Pb]Pb-MP0712, [203Pb]Pb-MP0712
- 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
- Medical subject headings
- Small Cell Lung Carcinoma, Carcinoma, Neuroendocrine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[212Pb]Pb-MP0712Drug
Also called [212Pb]Pb-DOTAM-MAM279
Radioligand Therapy
[203Pb]Pb-MP0712Other
Also called [203Pb]Pb-DOTAM-MAM279
Radioligand Imaging Agent
| Study group | Role | What they receive |
|---|---|---|
| [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 Receives: Drug: [212Pb]Pb-MP0712; Other: [203Pb]Pb-MP0712 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: until 5 years after last dose
To assess dose modifications of [212Pb]Pb-DOTAM-MAM279
Frequency and duration of dose changes
Measured: 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
Measured: 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
Measured: Phase 2a only; 12 months
Secondary outcomes (11)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: Phase 2a only; 12 months
To evaluate OS
Overall survival (OS) defined as the time from C1D1 to death from any cause
Measured: Phase 2a only; approx. 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2025
- Study start18 May 2026
- Primary completionSep 2028 (estimated)
- Study completionSep 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Large Cell Neuroendocrine CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Molecular Partners AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Orano Med LLC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07278479
- Sponsor's protocol ID
- MP0712-CP101
- Status last verified
- May 2026
- First submitted
- 10 Nov 2025
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided