Safety and Targeting of Anti-hk2 Antibody in mCRPC

Metastatic Disease Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04116164
• Other study ID #: GID5490
• Status: Terminated
• Phase: Early Phase 1
• Start date: September 18, 2019
• Est. completion date: July 6, 2023

Study information

• Verified date: September 2023
• Source: SpectronRX
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 27
• Est. completion date: July 6, 2023
• Est. primary completion date: July 6, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Castration-Resistant Prostatic Cancer
• Metastatic Disease
• Neoplasm Metastasis
• Prostatic Neoplasms
• Prostatic Neoplasms, Castration-Resistant

Intervention

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

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
SpectronRX	Invicro, Janssen Research & Development, LLC, Tomopath Inc.

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum pharmacokinetics	Serum clearance kinetics of 111In-DOTA-h11B6, only in cohort 1, at each mass amount of antibody (2, 10, and 20 mg).	6 months
Primary	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).	6 months
Primary	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.	9 months