Clinical trial NCT04116164: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Castration-Resistant Prostatic Cancer
Metastatic Disease
Keywords: Radiolabeled antibody
Imaging
Lead sponsor: SpectronRX
Sponsor class: INDUSTRY
Collaborators: name: Invicro
name: Janssen Research & Development, LLC
name: Tomopath Inc.
First posted: 2019-10-04
Enrollment: 27
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Serum pharmacokinetics
timeFrame: 6 months
measure: Radioactivity Biodistribution
timeFrame: 6 months
measure: Radioactivity accumulation in known tumor sites
timeFrame: 9 months
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Hospital for Cancer and Allied Diseases
name: Michael J Morris, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.
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.