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.
Trial Snapshot
- Phase
- Early Phase 1
- Status
- Terminated
- Sponsor
- SpectronRX
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- Serum pharmacokinetics
Study Overview
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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: 111In-DOTA-h11B6 (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
No secondary outcomes reported