Safety and Targeting of Anti-hk2 Antibody in mCRPC

• ClinicalTrials.gov Identifier: NCT04116164
• Recruitment Status: Unknown
• First Posted: October 4, 2019
• Last Update Posted: April 9, 2021
• Sponsor: Tomopath Inc.
• Collaborators: Invicro; Janssen Research & Development, LLC
• Information provided by (Responsible Party): Tomopath Inc.

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.

Condition or disease	Intervention/treatment	Phase
Castration-Resistant Prostatic Cancer; Metastatic Disease	Drug: 111In-DOTA-h11B6	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention 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)
• Primary Purpose: Other
• 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.
• Actual Study Start Date: September 18, 2019
• Estimated Primary Completion Date: December 30, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Serum pharmacokinetics [ Time Frame: 6 months ]
   Serum clearance kinetics of 111In-DOTA-h11B6, only in cohort 1, at each mass amount of antibody (2, 10, and 20 mg).
2. Radioactivity Biodistribution [ Time Frame: 6 months ]
   Radioactivity residence times in liver, kidneys and tumor, only in cohort 1, at each mass amount of antibody (2, 10, and 20 mg).
3. Radioactivity accumulation in known tumor sites [ Time Frame: 9 months ]
   Number of known metastatic lesions in which there is increased uptake of 111In, in both cohorts 1 and 2.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: The study is being carried out in prostate cancer which afflicts only men.
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Michael J Morris, MD; 646-497-9068; morrism@mskcc.org

Contact: Neeta Pandit-Taskar, MD; 212-639-3046; pandit-n@mskcc.org

Locations

United States, New York

Memorial Sloan-Kettering Cancer Center; Recruiting

New York, New York, United States, 10021

Contact: Michael J Morris, MD 646-497-9068 morrism@mskcc.org

Contact: Neeta Pandit-Taskar, MD 212-639-3049 pandit-n@mskcc.org

Sponsors and Collaborators

Tomopath Inc.

Invicro

Janssen Research & Development, LLC

Investigators

• Principal Investigator: Michael J Morris, MD; Memorial Hospital for Cancer and Allied Diseases

More Information

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.

Thorek DL, Watson PA, Lee SG, Ku AT, Bournazos S, Braun K, Kim K, Sjöström K, Doran MG, Lamminmäki 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.

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. Review.

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.

• Responsible Party: Tomopath Inc.
• ClinicalTrials.gov Identifier: NCT04116164
• Other Study ID Numbers: GID5490
• First Posted: October 4, 2019
• Last Update Posted: April 9, 2021
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tomopath Inc.:

Radiolabeled antibody; Imaging

Additional relevant MeSH terms:

Neoplasm Metastasis; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Neoplastic Processes; Neoplasms; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Prostatic Diseases