Study of 225Ac-ABD147 to Establish Optimal Dose in Patients With SCLC and LCNEC of the Lung That Previously Received Platinum-based Chemotherapy

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Large Cell Neuroendocrine Carcinoma of the Lung; Small-Cell Lung Cancer (SCLC)
• Intervention / Treatment: Drug: 225Ac-ABD147

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).

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • Santa Monica, California, United States, 90404
      • University of California, Los Angeles
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center, Univ of Miami
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists - Sarasota
  • Maryland
    • Glen Burnie, Maryland, United States, 21061
      • United Theranostics
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Has confirmed, locally advanced or metastatic SCLC or LCNEC of the lung.
• Has received 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 1.
• Expected life expectancy of >12 weeks per the Investigator.
• Has disease that is measurable by RECIST v1.1.
• 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, the patient must be sufficiently recovered and stable before the 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 by 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a Dose Escalation Group; 225Ac-ABD147 administered in escalating dose cohorts	Drug: 225Ac-ABD147; A delta-like ligand 3 (DLL3)-targeting antibody fragment conjugated with a linker-chelator that effectively coordinates Ac-225
Experimental: Phase 1b Dose Expansion Group; Expansion Dose Level selected from Phase 1a Dose Escalation	Drug: 225Ac-ABD147; A delta-like ligand 3 (DLL3)-targeting antibody fragment conjugated with a linker-chelator that effectively coordinates Ac-225

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ph 1a: Safety of 225Ac-ABD147 - Number and Grade of Adverse Events	Incidence of adverse events and serious adverse events graded according to NCI-CTCAE v5.0; Clinically significant changes from baseline for laboratory values, ECGs, and vital signs will be evaluated as adverse events.	12 months
Ph 1a: Tolerability of 225Ac-ABD147 - Number of Dose Limiting Toxicities	Incidence and nature of dose limiting toxicities.	12 months
Ph 1b: Safety of 225Ac-ABD147 to Determine the RP2D for Further Development - Number and Grade of Adverse Events	Incidence of adverse events and serious adverse events graded according to NCI-CTCAE v5.0; Clinically significant changes from baseline for laboratory values, ECGs, and vital signs will be evaluated as adverse events.	12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Overall Response Rate (ORR)	ORR of confirmed complete response (CR) and partial response (PR) per investigator assessment using RECIST v1.1.	12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Disease Control Rate (DCR)	DCR per investigator assessment using RECIST v1.1.	12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Duration of Response (DOR)	DOR of confirmed CR and PR per investigator assessment using RECIST v1.1.	12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Duration of Progression Free Survival (PFS)	PFS per investigator assessment using RECIST v1.1.	12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Overall Survival (OS)	OS.	12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - PFS Rate	6 monthly PFS rate per investigator assessment using RECIST v1.1.	12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - OS Rate	6 monthly OS rate.	12 months
Ph 1b: Biodistribution and Absorbed Dose - Measurement of Activity	Whole blood radioactivity with whole blood gamma counting.	6 months
Ph 1b: Immunogenicity of 225Ac-ABD147 - Measurement of Anti-drug Antibodies	Anti-drug antibody to ABD147.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ph 1a: Determination of 225Ac-ABD147 Dose for Expansion (Phase 1b)	The dose for expansion (Phase 1b) will be determined by integrating the totality of data obtained in Phase 1a.	12 months
Ph 1a: Safety and Tolerability of Multiples Doses of 225Ac-ABD147 - Number and Grade of Adverse Events	Incidence of adverse events and serious adverse events graded according to NCI-CTCAE v5.0; Clinically significant changes from baseline for laboratory values, ECGs, and vital signs will be evaluated as adverse events.	12 months
Ph 1a: PK Profile of 225Ac-ABD147 - Peak Plasma Concentration (Cmax)	Cmax.	6 months
Ph 1a: PK Profile of 225Ac-ABD147 - Area under the plasma concentration versus time curve (AUC)	AUC.	6 months
Ph 1a: PK Profile of 225Ac-ABD147 - Volume of Distribution (Vd)	Vd.	6 months
Ph 1a: PK Profile of 225Ac-ABD147 - Elimination	Half-life.	6 months
Ph 1a: PK Profile of 225Ac-ABD147 - Elimination	Clearance.	6 months
Ph 1a: Immunogenicity of 225Ac-ABD147 - Measurement of Anti-drug antibodies	Anti-drug antibody to ABD147.	6 months
Ph 1a: Safety of 111In-ABD147 - Number and Grade of Adverse Events	Incidence of adverse events and serious adverse events graded according to NCI-CTCAE v5.0.	2 weeks

Collaborators and Investigators

• Sponsor: Abdera Therapeutics Inc.
• Investigators: Study Director: Guanying Wang, MD, MS, Abdera Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: November 21, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): December 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Lung Cancer; Radiotherapy; Antibody; Biologic; Antibodies; Small Cell Lung Cancer; SCLC; Small-Cell Lung Cancer; DLL3; Delta Like Canonical Notch Ligand 3; Radioligand; Delta Like Protein 3; Radiopharmaceutical; Actinium; LCNEC; Large Cell Neuroendocrine Carcinoma; Ac-225; 225Ac-ABD147; Indium; In-111; 111In-ABD147; ABD147; Abdera Therapeutics; Abdera; ROVEr; Ac; In; ABD-147; Large-Cell Neuroendocrine Carcinoma; Delta-Like Ligand 3; Delta Like Ligand 3; Delta-Like Protein 3; Delta-Like Canonical Notch Ligand 3; Delta3; Precision Radiopharmaceutical; Linker-Chelator; Linker Chelator; VHH-Fc; HH-FcRN; Nuclide
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: 225Ac-ABD147-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No