Safety and Targeting of Anti-hk2 Antibody in mCRPC

NCT04116164 | Terminated Early Phase 1 FDA Drug

• 1 other identifier: GID5490
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Castration-Resistant Prostatic Cancer; Metastatic Disease

Keywords

Radiolabeled antibody; Imaging

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (1)

Dosimetry and targeting

EXPERIMENTAL

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

Interventions

111In-DOTA-h11B6 DRUG

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

Dosimetry and targeting

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: The study is being carried out in prostate cancer which afflicts only men.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• SpectronRX: lead
• Invicro: collaborator
• Janssen Research & Development, LLC: collaborator
• Tomopath Inc.: collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Related 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.

  PMID: 9187691 BACKGROUND

• 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.

  PMID: 27903863 BACKGROUND

• 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.

  PMID: 23903407 BACKGROUND

• 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.

  PMID: 26983637 BACKGROUND

• 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.

  PMID: 29691406 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael J Morris, MD

  Memorial Hospital for Cancer and Allied Diseases

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 1, 2019
• First Posted: October 4, 2019
• Study Start: September 18, 2019
• Primary Completion: July 6, 2023
• Study Completion: July 6, 2023
• Last Updated: September 25, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)