Clinical trial NCT06736418: Study of 225Ac-ABD147 to Establish Optimal Dose in Patients With SCLC and LCNEC of the Lung That Previously Received Platinum-based Chemotherapy
Official title: A Phase 1a/b, Open-label, Dose-escalation Study of the Safety, Pharmacokinetics, and Initial Efficacy of 225Ac-ABD147 in Patients With Small Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma of the Lung Following Platinum-based Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Small-Cell Lung Cancer (SCLC)
Large Cell Neuroendocrine Carcinoma of the Lung
Keywords: Actinium
Ac-225
225Ac-ABD147
Indium
In-111
111In-ABD147
ABD147
Abdera Therapeutics
Abdera
ROVEr
Ac
In
ABD-147
Small Cell Lung Cancer
Small-Cell Lung Cancer
SCLC
Large Cell Neuroendocrine Carcinoma
Large-Cell Neuroendocrine Carcinoma
LCNEC
Lung Cancer
Delta-Like Ligand 3
Delta Like Ligand 3
Delta-Like Protein 3
Delta Like Protein 3
Delta-Like Canonical Notch Ligand 3
Delta Like Canonical Notch Ligand 3
Delta3
DLL3
Precision Radiopharmaceutical
Radiopharmaceutical
Radiotherapy
Radioligand
Linker-Chelator
Linker Chelator
VHH-Fc
HH-FcRN
Biologic
Antibody
Antibodies
Nuclide
Lead sponsor: Abdera Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2024-12-16
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose Escalation and Dose Expansion
Primary purpose: TREATMENT

Brief summary: The study has 2 parts, Phase 1a and Phase 1b. The goal of Phase 1a is to gather safety, PK and initial efficacy data for 225Ac-ABD147 to better understand best doses for patients with small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung following platinum-based chemotherapy.

An initial group of patients will also be given an experimental imaging agent called 111In-ABD147 to help understand where ABD147 goes in the body.

The goal of Phase 1b is to gather additional safety and efficacy data on 225Ac-ABD147 to determine the best dose and to understand how those doses affect the same types of patients' cancers explored enrolled in Phase 1a.

Detailed description: This is an open-label, Phase 1a/b, first-in-human study to assess the safety profile, tolerability, biodistribution, pharmacokinetics (PK), and preliminary antitumor activity of 225Ac-ABD147 in patients with confirmed locally advanced or metastatic small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung. All patients must have previously received platinum-based chemotherapy.

Phase 1a will determine the safety, tolerability, dosimetry, PK, and the dose of 225Ac-ABD147 for expansion in the Phase 1b portion.

In addition to receiving treatment, a subset of patients in Phase 1a will undergo either 111In-ABD147-based or 225Ac-ABD147 dosimetry assessments to confirm tumor specificity, identify biodistribution, and to provide insight into dose absorption into tumor and normal tissues.

Phase 1b will evaluate the safety and preliminary efficacy of 225Ac-ABD147 as based on the Phase 1a dose level for expansion by the Safety Review Committee to determine the recommended Phase 2 dose (RP2D).

Eligibility criteria: Key Inclusion Criteria:

* Has confirmed, locally advanced or metastatic SCLC or LCNEC of the lung.
* Has completed platinum-based chemotherapy.
* Mentally competent and able to understand and sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved Informed Consent Form (ICF)prior to any study specific evaluation.
* Age ≥18 years old at the time the ICF is signed.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
* Expected life expectancy of \>12 weeks per the Investigator.
* Has disease that is measurable by RECIST v 1.1.
* Patients with known brain metastases are eligible provided they are considered by the Investigator to be neurologically stable and meet the following criteria: a. Radiotherapy or surgery for brain metastases was completed at least 2 weeks prior to Cycle 1 Day 1 (C1D1); b. Symptoms are stable and steroid/antiepileptic doses remain unchanged for a minimum of 2 weeks prior to C1D1.
* At least 4 weeks from prior major surgery (other than for brain metastases), or at least 7 days from prior non-study-related minor surgery prior to C1D1. In all cases, patient must be sufficiently recovered and stable before study treatment administration.
* Willing to provide archival tumor tissue for central analysis; if unavailable, a pre-study treatment biopsy may be collected and provided.
* Female and male patients of childbearing potential agree to use at least 2 highly effective forms of contraception (1 at least must be barrier method) or agree to completely remain abstinent for duration of study and for 6 months after the last administration of study drug for both female patients and male patients.
* Patients agree to not make semen/egg donations during treatment, within 2 weeks following the last dose of 111In-ABD147, and for 6 months following the last dose of 225Ac-ABD147.

Key Exclusion Criteria:

* Was previously treated with 225Ac-ABD147.
* Has a history of steroid dependent hepatitis caused by treatment with a checkpoint inhibitor.
* Is actively enrolled in another clinical study unless it is an observational (noninterventional) clinical study or the follow-up component of an interventional study.
* Use of an anticancer therapy, radiotherapy (external beam radiotherapy \[EBRT\], brachytherapy, inoperative radiation therapy, radiopharmaceuticals), or immunotherapy within 3 weeks prior to C1D1. Prior treatment with DLL3-targeting agent is acceptable with appropriate washout.
* Has a medical history of myocardial infarction or unstable angina within 6 months before C1D1.
* Has clinically significant cardiac disease not controlled on medical therapy (eg, congestive cardiac failure, arrhythmia, coronary heart disease).
* Has evidence of active infection requiring intravenous (IV) antibiotics during Screening requiring therapy within 7 days prior to C1D1.
* Has active uncontrolled bleeding or a bleeding diathesis within 28 days prior to C1D1.
* Has serious or non-healing wound, fistula, skin ulcer, or non-healing bone fracture within 7 days prior to C1D1.
* Has received any thoracic radiotherapy within 8 weeks prior to C1D1.
* Has a history of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis (requiring steroids or immunosuppressive agents), or idiopathic pneumonitis, or evidence of active pneumonitis on the Screening chest computed tomography (CT) scan. Note: History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
* Has known hypersensitivity to Ac-225; for patients participating in the 111In-ABD147 dosimetry substudy, also has known hypersensitivity to In-111.
* Has known hypersensitivity to Chinese hamster ovary cell products.
* Has a history of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
* Has human immunodeficiency virus infection; patients who are taking an effective antiviral therapy with undetectable viral load prior to C1D1 are eligible.
* Has chronic hepatitis B virus (HBV) infection. Patients who are taking an effective suppressive therapy and have an undetectable HBV viral load are eligible.
* Has a history of hepatitis C virus (HCV) infection, unless treated and cured; patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible.
* Has carcinomatous meningitis.
* Has active symptomatic cord compression.
* Has active symptomatic superior vena cava syndrome.
* Has another primary malignancy that has not been treated with curative intent (discuss with Medical Monitor), except for non-metastatic cutaneous basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer.
* Is unwilling or unable to follow protocol requirements.
* Has any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of the patient's safety or study results.

Primary outcomes:
measure: Ph 1a: Safety of 225Ac-ABD147 - Number and Grade of Adverse Events
timeFrame: 12 months
measure: Ph 1a: Tolerability of 225Ac-ABD147 - Number of Dose Limiting Toxicities
timeFrame: 12 months
measure: Ph 1b: Safety of 225Ac-ABD147 to Determine the RP2D for Further Development - Number and Grade of Adverse Events
timeFrame: 12 months
measure: Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Overall Response Rate (ORR)
timeFrame: 12 months
measure: Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Disease Control Rate (DCR)
timeFrame: 12 months
measure: Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Duration of Response (DOR)
timeFrame: 12 months
measure: Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Duration of Progression Free Survival (PFS)
timeFrame: 12 months
measure: Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Overall Survival (OS)
timeFrame: 12 months
measure: Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - PFS Rate
timeFrame: 12 months
measure: Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - OS Rate
timeFrame: 12 months
measure: Ph 1b: Biodistribution and Absorbed Dose - Measurement of Activity
timeFrame: 6 months
measure: Ph 1b: Immunogenicity of 225Ac-ABD147 - Measurement of Anti-drug Antibodies
timeFrame: 6 months
Secondary outcomes:
measure: Ph 1a: Determination of 225Ac-ABD147 Dose for Expansion (Phase 1b)
timeFrame: 12 months
measure: Ph 1a: Safety and Tolerability of Multiples Doses of 225Ac-ABD147 - Number and Grade of Adverse Events
timeFrame: 12 months
measure: Ph 1a: PK Profile of 225Ac-ABD147 - Peak Plasma Concentration (Cmax)
timeFrame: 6 months
measure: Ph 1a: PK Profile of 225Ac-ABD147 - Area under the plasma concentration versus time curve (AUC)
timeFrame: 6 months
measure: Ph 1a: PK Profile of 225Ac-ABD147 - Volume of Distribution (Vd)
timeFrame: 6 months
measure: Ph 1a: PK Profile of 225Ac-ABD147 - Elimination
timeFrame: 6 months
measure: Ph 1a: PK Profile of 225Ac-ABD147 - Elimination
timeFrame: 6 months
measure: Ph 1a: Immunogenicity of 225Ac-ABD147 - Measurement of Anti-drug antibodies
timeFrame: 6 months
measure: Ph 1a: Safety of 111In-ABD147 - Number and Grade of Adverse Events
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Glen Burnie
country: United States
facility: United Theranostics
state: Maryland
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: MD Anderson
state: Texas
Study officials:
affiliation: Abdera Therapeutics Inc.
name: Guanying Wang, MD, MS
role: STUDY_DIRECTOR
References: