Safety and Targeting of Anti-hk2 Antibody in mCRPC

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.

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Disease; Castration-Resistant Prostatic Cancer
• Intervention / Treatment: Drug: 111In-DOTA-h11B6

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Neeta Pandit-Taskar, MD; Phone Number: 212-639-3046; Email: pandit-n@mskcc.org
• Study Contact Backup: Name: Michael J Morris, MD; Phone Number: 646-497-9068; Email: morrism@mskcc.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dosimetry and targeting; 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	Drug: 111In-DOTA-h11B6; 4-6 mCi 111In labeled to 2 mg DOTA-h11B6; 0, 8 or 18 mg additional h11B6.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: SpectronRX
• Collaborators: Janssen Research & Development, LLC; Invicro; Tomopath Inc.
• Investigators: Principal Investigator: Michael J Morris, MD, Memorial Hospital for Cancer and Allied Diseases

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2019
• Primary Completion (Actual): July 6, 2023
• Study Completion (Actual): July 6, 2023

Study Registration Dates

• First Submitted: October 1, 2019
• First Submitted That Met QC Criteria: October 2, 2019
• First Posted (Actual): October 4, 2019

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Imaging; Radiolabeled antibody
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Neoplasm Metastasis; Prostatic Neoplasms, Castration-Resistant
• Other Study ID Numbers: GID5490

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No