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.

Tracking Information

• First Submitted Date: October 1, 2019
• First Posted Date: October 4, 2019
• Last Update Posted Date: April 9, 2021
• Actual Study Start Date: September 18, 2019
• Estimated Primary Completion Date: December 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2019)

• 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).
• 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).
• 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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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.

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.

• Study Type: Interventional
• Study Phase: Early Phase 1

Study Design

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

Condition

• Castration-Resistant Prostatic Cancer
• Metastatic Disease

Intervention

Drug: 111In-DOTA-h11B6

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

Study Arms

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

Intervention: Drug: 111In-DOTA-h11B6

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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: October 2, 2019): 18
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2021
• Estimated Primary Completion Date: December 30, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• 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.

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04116164
• Other Study ID Numbers: GID5490
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Tomopath Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Tomopath Inc.
• Original Study Sponsor: Same as current

Collaborators

• Invicro
• Janssen Research & Development, LLC

Investigators

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

• PRS Account: Tomopath Inc.
• Verification Date: October 2020