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

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.

Eligibility Criteria

Ages Eligible for Study:
18 Years and older

Genders Eligible for Study:
All

Accepts Healthy Volunteers:
No

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.