Imaging of Solid Tumors Using DLL3 SPECT

Thomas Hope

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Solid Tumor Cancer; Castration Resistant Prostate Cancer (CRPC); Neuroendocrine (NE) Tumors; Castration Resistant Prostate Cancer

Treatments: Drug: 111In-ABD147; Procedure: Single-photon emission computed tomography (SPECT)/Computerized tomography (CT)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07052760

NCI-2025-04590 (Registry Identifier)

25926

Details and patient eligibility

About

This is a single arm, pilot trial that evaluates the ability of a novel imaging agent (111In-ABD147) to detect metastatic cancer in participants with solid tumors. 111In-ABD147 is a high affinity Delta-like ligand 3 (DLL3) antigen binding domain fused to an engineered humanized Fc to create an antibody (VHH-Fc) that is bio-conjugated with a DOTA linker-chelator to a 111In radiometal. DLL3 is expressed on a variety of tumors, particularly those with neuroendocrine features.

Full description

PRIMARY OBJECTIVE:

1) Determine the feasibility of detecting tumor uptake using 111In-ABD147.

SECONDARY OBJECTIVE:

1) Safety of 111In-ABD147.

EXPLORATORY OBJECTIVES:

1. Correlation of 111In-ABD147 uptake with DLL3 expression determined by immunohistochemistry.
2. Compare 111In-ABD147 scan results to archival Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) images when available.

OUTLINE:

Participants will be assigned to cohorts based on solid tumor diagnosis. All participants will receive 1 dose of study drug followed by single-photon emission computed tomography (SPECT)/Computerized tomography (CT) imaging. Repeat administration of 111In-ABD147 and SPECT/CT imaging may be performed. Participants will be followed for up to 7 days after last dose for safety.

Enrollment: 45 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years

2. Histopathologically confirmed solid tumors in one of the following cohorts:

   1. Cohort 1 (n=15): Histologically confirmed prostate cancer, with castration resistant disease per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria.
   2. Cohort 2 (n=15): Histologically confirmed high grade neuroendocrine tumor, with a Ki-67 over 20.
   3. Cohort 3 (n=15): Agnostic to tumor type.

3. Metastatic disease present on conventional imaging defined as having Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 measurable disease or multiple bone metastases.

4. Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion criteria

1. Unlikely to comply with protocol procedures, restrictions and requirements and judged by the Investigator to be unsuitable for participation.
2. Has known hypersensitivity to Chinese hamster ovary cell products.
3. Has a history of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
4. Known pregnancy.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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45 participants in 3 patient groups

Cohort 1: Castration resistant prostate cancer

Experimental group

Description:

Participants will receive a single administration of 185 megabecquerels (MBq) (5 millicurie (mCi)) +/- 10% of 111In-ABD147 prior to SPECT/CT imaging 48 hours after injection. Repeat administration of 111In-ABD147 and SPECT/CT imaging may be performed. Participants will be followed for up to 7 days after the injection of 111In-ABD147 for evaluation of adverse events.

Treatment:

Procedure: Single-photon emission computed tomography (SPECT)/Computerized tomography (CT)

Drug: 111In-ABD147

Cohort 2: High grade neuroendocrine tumor

Experimental group

Description:

Participants will receive a single administration of 185 MBq (5 mCi) +/- 10% of 111In-ABD147 prior to SPECT/CT imaging 48 hours after injection. Repeat administration of 111In-ABD147 and SPECT/CT imaging may be performed. Participants will be followed for up to 7 days after the injection of 111In-ABD147 for evaluation of adverse events.

Treatment:

Procedure: Single-photon emission computed tomography (SPECT)/Computerized tomography (CT)

Drug: 111In-ABD147

Cohort 3: Agnostic solid tumors

Experimental group

Description:

Participants will receive a single administration of 185 MBq (5 mCi) +/- 10% of 111In-ABD147 prior to SPECT/CT imaging 48 hours after injection. Repeat administration of 111In-ABD147 and SPECT/CT imaging may be performed. Participants will be followed for up to 7 days after the injection of 111In-ABD147 for evaluation of adverse events.

Treatment:

Procedure: Single-photon emission computed tomography (SPECT)/Computerized tomography (CT)

Drug: 111In-ABD147