DLL3-targeted alpha radiotherapy ([212Pb]Pb-MP0712) for advanced small cell lung cancer and DLL3-positive neuroendocrine 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
This will test a DLL3-targeted radioactive drug ([212Pb]Pb-MP0712) to see if it's safe and can shrink tumors in adults with advanced small cell lung cancer or other DLL3-positive neuroendocrine cancers.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 138 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Molecular Partners AG Industry-sponsored |
| Drugs / interventions | immunotherapy |
| Locations | 3 sites (Glen Burnie, Maryland and 2 other locations) |
| Trial ID | NCT07278479 on ClinicalTrials.gov |
What this trial studies
This Phase 1/2a open-label, multicenter trial uses dose escalation followed by dose expansion to study [212Pb]Pb-MP0712 in adults with SCLC and other DLL3-expressing solid tumors. The trial collects safety, tolerability, dosimetry, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity data. [203Pb]Pb-MP0712 SPECT/CT imaging is used for DLL3 detection and dosimetry, and prior DLL3-targeted therapy is permitted in some cohorts. Serial imaging and blood sampling will characterize biodistribution and radiation dose to normal tissues and tumors.
Who should consider this trial
Good fit: Adults (≥18) with histologically or cytologically confirmed SCLC, lung large cell neuroendocrine carcinoma, or other DLL3-positive extrapulmonary neuroendocrine carcinomas who have progressed after prior systemic therapy and meet organ-function and imaging requirements are eligible.
Not a fit: Patients whose tumors do not express DLL3, who have poor organ function, or who cannot undergo radiopharmaceutical dosing or required imaging are unlikely to receive benefit from this approach.
Why it matters
Potential benefit: If successful, this targeted alpha radiotherapy could provide a new option that delivers potent, tumor-focused radiation to DLL3-expressing cancers and potentially shrink tumors that have failed standard treatments.
How similar studies have performed: DLL3-targeted antibody-drug conjugates produced mixed or negative clinical results, and DLL3-directed alpha radiopharmaceuticals are a novel approach with limited clinical outcome data so far.
Eligibility criteria
Show full inclusion / 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.
Where this trial is running
Glen Burnie, Maryland and 2 other locations
- United Theranostics — Glen Burnie, Maryland, United States (Recruiting)
- Nebraska Cancer Specialists — Omaha, Nebraska, United States (Recruiting)
- United Theranostics — Princeton, New Jersey, United States (Recruiting)
Study contacts
- Study coordinator: Medical Director MPAG
- Email: info@molecularpartners.com
- Phone: +41 44 755 77 00
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.