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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
65
A delta-like ligand 3 (DLL3)-targeting antibody fragment conjugated with a linker-chelator that effectively coordinates Ac-225
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States
RECRUITINGUnited Theranostics
Glen Burnie, Maryland, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITINGMD Anderson
Houston, Texas, United States
RECRUITINGHuntsman Cancer Institute
Salt Lake City, Utah, United States
RECRUITINGPh 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.
Time frame: 12 months
Ph 1a: Tolerability of 225Ac-ABD147 - Number of Dose Limiting Toxicities
Incidence and nature of dose limiting toxicities.
Time frame: 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.
Time frame: 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.
Time frame: 12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Disease Control Rate (DCR)
DCR per investigator assessment using RECIST v1.1.
Time frame: 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.
Time frame: 12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Duration of Progression Free Survival (PFS)
PFS per investigator assessment using RECIST v1.1.
Time frame: 12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Overall Survival (OS)
OS.
Time frame: 12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - PFS Rate
6 monthly PFS rate per investigator assessment using RECIST v1.1.
Time frame: 12 months
Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - OS Rate
6 monthly OS rate.
Time frame: 12 months
Ph 1b: Biodistribution and Absorbed Dose - Measurement of Activity
Whole blood radioactivity with whole blood gamma counting.
Time frame: 6 months
Ph 1b: Immunogenicity of 225Ac-ABD147 - Measurement of Anti-drug Antibodies
Anti-drug antibody to ABD147.
Time frame: 6 months
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.
Time frame: 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.
Time frame: 12 months
Ph 1a: PK Profile of 225Ac-ABD147 - Peak Plasma Concentration (Cmax)
Cmax.
Time frame: 6 months
Ph 1a: PK Profile of 225Ac-ABD147 - Area under the plasma concentration versus time curve (AUC)
AUC.
Time frame: 6 months
Ph 1a: PK Profile of 225Ac-ABD147 - Volume of Distribution (Vd)
Vd.
Time frame: 6 months
Ph 1a: PK Profile of 225Ac-ABD147 - Elimination
Half-life.
Time frame: 6 months
Ph 1a: PK Profile of 225Ac-ABD147 - Elimination
Clearance.
Time frame: 6 months
Ph 1a: Immunogenicity of 225Ac-ABD147 - Measurement of Anti-drug antibodies
Anti-drug antibody to ABD147.
Time frame: 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.
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Time frame: 2 weeks