DLL3-targeted alpha radiotherapy ([212Pb]Pb-MP0712) for advanced small cell lung cancer and DLL3-positive neuroendocrine tumors

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Moffitt Cancer Center
  Tampa, Florida, United States Recruiting
• Emory University Hospital
  Atlanta, Georgia, United States Recruiting
• University of Chicago
  Chicago, Illinois, United States Recruiting
• 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

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.