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
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Molecular Partners AG
- Enrollment
- 138
- Locations
- 3
- Primary Endpoint
- To assess incidence and severity of safety events following administration of [212Pb]Pb-DOTAM-MAM279
Overview
Brief 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.
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
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.
Arms & Interventions
[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
Intervention: [212Pb]Pb-MP0712 (Drug)
[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
Intervention: [203Pb]Pb-MP0712 (Other)
Outcomes
Primary Outcomes
To assess incidence and severity of safety events following administration of [212Pb]Pb-DOTAM-MAM279
Time Frame: until 5 years after last dose
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)
To assess dose modifications of [212Pb]Pb-DOTAM-MAM279
Time Frame: until 5 years after last dose
Frequency and duration of dose changes
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
Time Frame: Phase 1, from start of treatment to end of first cycle (day 1 - 28)
Incidence of dose limiting toxicities
To evaluate the preliminary anti-tumor activity of [212Pb]Pb-DOTAM-MAM279 in the dose expansion part
Time Frame: Phase 2a only; 12 months
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
Secondary Outcomes
- To assess 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 evaluate DCR(Phase 2a only; 12 months)
- To assess 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 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 evaluate PFS(Phase 2a only; 12 months)
- To evaluate DoR(Phase 2a only; 12 months)
- To assess the area under the curve (AUC) from time 0 to the time of the last quantifiable concentration of [203Pb]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(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(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(up to 10 days following [203Pb]Pb-DOTAM-MAM279 administration)
- To evaluate OS(Phase 2a only; approx. 5 years)