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Safety and Targeting of Anti-hk2 Antibody in mCRPC

Primary Purpose

Castration-Resistant Prostatic Cancer, Metastatic Disease

Status

Terminated

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

111In-DOTA-h11B6

About this trial

This is an interventional other trial for Castration-Resistant Prostatic Cancer focused on measuring Radiolabeled antibody, Imaging

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Subjects with mCRPC will be eligible if they meet the following criteria:
Eastern Cooperative Oncology Group (ECOG) ≤ 1
Histologically or cytologically confirmed adenocarcinoma of the prostate
Castrate levels of testosterone (<50 ng/dL [1.74 nmol/L])
Metastatic disease documented by imaging
Documented progressive mCRPC with androgen involvement as defined by - Prostate Cancer Working Group 3
Acceptable laboratory parameters
At least 28 days since administration of any therapeutic radioactive isotope
Able to tolerate the conditions required to perform imaging studies (e.g., lying flat for at least 1 hour).

Exclusion Criteria:

Known hypersensitivity to proteins, or other allergic diathesis that, in the opinion of the investigator, makes an immune response to humanized antibody likely
Radiotherapy or immunotherapy within 30 days, or single fraction of palliative radiotherapy within 14 days of administration of study agent
Any condition that, in the opinion of the Investigator, would impair the subject's ability to comply with study procedures and required study visits
Active, symptomatic, or untreated brain metastases.

Sites / Locations

Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dosimetry and targeting

Arm Description

Three sub-cohorts in cohort 1 will receive one slow bolus IV injection of 2 mg 111In-DOTA-h11B6 with 0, 8 and 18 mg unlabeled h11B6 respectively. In cohort 2, up to 6 patients will receive a slow bolus IV injection of 2 mg 111In-DOTA_h11B6 with any unlabeled h11B6 as determined from cohort 1, and will be imaged at one time-point

Outcomes

Primary Outcome Measures

Serum pharmacokinetics

Serum clearance kinetics of 111In-DOTA-h11B6, only in cohort 1, at each mass amount of antibody (2, 10, and 20 mg).

Radioactivity Biodistribution

Radioactivity residence times in liver, kidneys and tumor, only in cohort 1, at each mass amount of antibody (2, 10, and 20 mg).

Radioactivity accumulation in known tumor sites

Number of known metastatic lesions in which there is increased uptake of 111In, in both cohorts 1 and 2.

Secondary Outcome Measures

Full Information

NCT ID

NCT04116164

First Posted

October 1, 2019

Last Updated

September 21, 2023

Sponsor

SpectronRX

Collaborators

Invicro, Janssen Research & Development, LLC, Tomopath Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04116164

Brief Title

Safety and Targeting of Anti-hk2 Antibody in mCRPC

Official Title

A Phase 0 Study to Assess the Safety and Biodistribution of a Novel Radiolabeled Antibody Targeting Human Kallikrein-2 (hk2) in Subjects With Metastatic Castration-resistant Prostate Cancer.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Terminated

Why Stopped

Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention

Study Start Date

September 18, 2019 (Actual)

Primary Completion Date

July 6, 2023 (Actual)

Study Completion Date

July 6, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

SpectronRX

Collaborators

Invicro, Janssen Research & Development, LLC, Tomopath Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is an imaging trial, to develop h11B6 as a therapeutic radiopharmaceutical for men with mCRPC. This imaging study will be conducted to confirm the safety and estimate the mass amount of antibody h11B6, and confirm in vivo tumor targeting of the antibody, using Indium-111 (111In) radiolabeled h11B6 in subjects with advanced prostate cancer. This study will also provide the dosimetric information crucial for Phase 1 therapy.

Detailed Description

It is the intent to develop h11B6 as a therapeutic radiopharmaceutical for men with mCRPC. This Phase 0 study will be conducted to confirm the safety, estimate the mass amount, and confirm in vivo tumor targeting of the antibody. This study will use Indium-111 (111In) radiolabeled h11B6 in subjects with mCRPC to image known sites of disease and identify a favorable mass amount of antibody for satisfactory tumor targeting with minimal/no accumulation off-target. In cohort 1, In-111 labeled h11B6 will remain fixed at 2 mg, and additional h11B6 will be added in 2 sub-cohorts (8 mg and 18 mg respectively); up to 6 patients may be entered into a sub-cohort. Additional patients (up to 6) will be studied once the most favorable mass and imaging time point have been established, to establish targeting of antibody to known disease. This study will provide the dosimetric information crucial for Phase 1 therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Castration-Resistant Prostatic Cancer, Metastatic Disease

Keywords

Radiolabeled antibody, Imaging

7. Study Design

Primary Purpose

Other

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Model Description

3-6 patients will be studied in each of 3 sub-cohorts to determine the most favorable mass amount of h11B6 (2 mg, 10 mg, 20 mg). An additional 6 patients will be imaged at the most favorable mass amount to assess tumor targeting.

Masking

None (Open Label)

Allocation

N/A

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dosimetry and targeting

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

111In-DOTA-h11B6

Intervention Description

4-6 mCi 111In labeled to 2 mg DOTA-h11B6; 0, 8 or 18 mg additional h11B6.

Primary Outcome Measure Information:

Title

Serum pharmacokinetics

Description

Serum clearance kinetics of 111In-DOTA-h11B6, only in cohort 1, at each mass amount of antibody (2, 10, and 20 mg).

Time Frame

6 months

Title

Radioactivity Biodistribution

Description

Radioactivity residence times in liver, kidneys and tumor, only in cohort 1, at each mass amount of antibody (2, 10, and 20 mg).

Time Frame

6 months

Title

Radioactivity accumulation in known tumor sites

Description

Number of known metastatic lesions in which there is increased uptake of 111In, in both cohorts 1 and 2.

Time Frame

9 months

10. Eligibility

Sex

Male

Gender Based

Yes

Gender Eligibility Description

The study is being carried out in prostate cancer which afflicts only men.

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects with mCRPC will be eligible if they meet the following criteria: Eastern Cooperative Oncology Group (ECOG) ≤ 1 Histologically or cytologically confirmed adenocarcinoma of the prostate Castrate levels of testosterone (<50 ng/dL [1.74 nmol/L]) Metastatic disease documented by imaging Documented progressive mCRPC with androgen involvement as defined by - Prostate Cancer Working Group 3 Acceptable laboratory parameters At least 28 days since administration of any therapeutic radioactive isotope Able to tolerate the conditions required to perform imaging studies (e.g., lying flat for at least 1 hour). Exclusion Criteria: Known hypersensitivity to proteins, or other allergic diathesis that, in the opinion of the investigator, makes an immune response to humanized antibody likely Radiotherapy or immunotherapy within 30 days, or single fraction of palliative radiotherapy within 14 days of administration of study agent Any condition that, in the opinion of the Investigator, would impair the subject's ability to comply with study procedures and required study visits Active, symptomatic, or untreated brain metastases.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael J Morris, MD

Organizational Affiliation

Memorial Hospital for Cancer and Allied Diseases

Official's Role

Principal Investigator

Facility Information:

Facility Name

Memorial Sloan-Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

9187691

Citation

Darson MF, Pacelli A, Roche P, Rittenhouse HG, Wolfert RL, Young CY, Klee GG, Tindall DJ, Bostwick DG. Human glandular kallikrein 2 (hK2) expression in prostatic intraepithelial neoplasia and adenocarcinoma: a novel prostate cancer marker. Urology. 1997 Jun;49(6):857-62. doi: 10.1016/s0090-4295(97)00108-8.

Results Reference

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PubMed Identifier

27903863

Citation

Thorek DL, Watson PA, Lee SG, Ku AT, Bournazos S, Braun K, Kim K, Sjostrom K, Doran MG, Lamminmaki U, Santos E, Veach D, Turkekul M, Casey E, Lewis JS, Abou DS, van Voss MR, Scardino PT, Strand SE, Alpaugh ML, Scher HI, Lilja H, Larson SM, Ulmert D. Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis. Sci Transl Med. 2016 Nov 30;8(367):367ra167. doi: 10.1126/scitranslmed.aaf2335.

Results Reference

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PubMed Identifier

23903407

Citation

Thorek DL, Evans MJ, Carlsson SV, Ulmert D, Lilja H. Prostate-specific kallikrein-related peptidases and their relation to prostate cancer biology and detection. Established relevance and emerging roles. Thromb Haemost. 2013 Sep;110(3):484-92. doi: 10.1160/TH13-04-0275. Epub 2013 Aug 1.

Results Reference

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PubMed Identifier

26983637

Citation

Vilhelmsson Timmermand O, Larsson E, Ulmert D, Tran TA, Strand S. Radioimmunotherapy of prostate cancer targeting human kallikrein-related peptidase 2. EJNMMI Res. 2016 Dec;6(1):27. doi: 10.1186/s13550-016-0181-z. Epub 2016 Mar 17.

Results Reference

background

PubMed Identifier

29691406

Citation

McDevitt MR, Thorek DLJ, Hashimoto T, Gondo T, Veach DR, Sharma SK, Kalidindi TM, Abou DS, Watson PA, Beattie BJ, Timmermand OV, Strand SE, Lewis JS, Scardino PT, Scher HI, Lilja H, Larson SM, Ulmert D. Feed-forward alpha particle radiotherapy ablates androgen receptor-addicted prostate cancer. Nat Commun. 2018 Apr 24;9(1):1629. doi: 10.1038/s41467-018-04107-w.

Results Reference

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Safety and Targeting of Anti-hk2 Antibody in mCRPC

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