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

NCT06736418 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 225Ac-ABD147-101
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 12

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.

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

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (9)

• Ph 1a: Determination of 225Ac-ABD147 Dose for Expansion (Phase 1b)

  12 months

• Ph 1a: Safety and Tolerability of Multiples Doses of 225Ac-ABD147 - Number and Grade of Adverse Events

  12 months

• Ph 1a: PK Profile of 225Ac-ABD147 - Peak Plasma Concentration (Cmax)

  6 months

• Ph 1a: PK Profile of 225Ac-ABD147 - Area under the plasma concentration versus time curve (AUC)

  6 months

• Ph 1a: PK Profile of 225Ac-ABD147 - Volume of Distribution (Vd)

  6 months

Study Arms (2)

Phase 1a Dose Escalation Group

EXPERIMENTAL

225Ac-ABD147 administered in escalating dose cohorts

Drug: 225Ac-ABD147

Phase 1b Dose Expansion Group

EXPERIMENTAL

Expansion Dose Level selected from Phase 1a Dose Escalation

Drug: 225Ac-ABD147

Interventions

225Ac-ABD147 DRUG

A delta-like ligand 3 (DLL3)-targeting antibody fragment conjugated with a linker-chelator that effectively coordinates Ac-225

Phase 1a Dose Escalation Group; Phase 1b Dose Expansion Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abdera Therapeutics Inc.: lead

Study Sites (12)

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of California, Los Angeles

Santa Monica, California, 90404, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Sylvester Comprehensive Cancer Center, Univ of Miami

Miami, Florida, 33136, United States

Location

Florida Cancer Specialists - Sarasota

Sarasota, Florida, 34232, United States

Location

United Theranostics

Glen Burnie, Maryland, 21061, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Lung Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Guanying Wang, MD, MS

  Abdera Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation and Dose Expansion

Study Record Dates

• First Submitted: November 21, 2024
• First Posted: December 16, 2024
• Study Start: March 10, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (12)