A Study of the Safety and Pharmacokinetics of Escalating Doses of DSTP3086S in Patients With Metastatic Castration-Resistant Prostate Cancer

A Phase I, Open-Label Study of the Safety and Pharmacokinetics of Escalating Doses of DSTP3086S in Patients With Metastatic Castration-Resistant Prostate Cancer

This is a Phase I, multicenter, open-label, dose-escalation study of DSTP3086S administered as a single agent by intravenous (IV) infusion to patients with metastatic Castration-Resistant Prostate Cancer (CRPC).

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: DSTP3086S; Drug: DSTP3086S

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Michigan
    • Detroit, Michigan, United States, 48201
  • New York
    • New York, New York, United States, 10065
  • Washington
    • Seattle, Washington, United States, 98195

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy of at least 12 weeks
• Histologic documentation of adenocarcinoma of the prostate
• Surgical castration or ongoing use of gonadotropin-releasing hormone agonists with confirmed castrate levels of testosterone
• Metastatic progressive CRPC defined as progressive disease despite surgical castration or ongoing use of gonadotropin-releasing hormone agonists with confirmed castrate levels of testosterone
• For patients in the dose-expansion cohort of the study, not more than two prior lines of cytotoxic chemotherapy in the metastatic setting
• Evaluable or measurable disease
• Documented willingness to use an effective means of contraception

Exclusion Criteria:

• Anti-tumor therapy, including chemotherapy, biologic, experimental, or hormonal therapy, or radiotherapy within 4 weeks prior to Day 1, with the following exceptions: maintenance hormonal therapy for metastatic prostate cancer and palliative radiation to bone metastases within 2 weeks prior to Day 1
• Major surgical procedure within 4 weeks prior to Day 1
• Known active bacterial, viral, fungal, mycobacterial, or other infection (including HIV and atypical mycobacterial disease, but excluding fungal infections of the nail beds)
• Ongoing corticosteroid use with > 10 mg of daily prednisone or equivalent
• Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy. Patients who are receiving bisphosphonate therapy specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Untreated or active central nervous system (CNS) metastases. Patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria: evaluable or measurable disease outside the CNS, radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study, and screening CNS radiographic study is >/= 8 weeks since completion of radiotherapy and >/= 4 weeks since the discontinuation of corticosteroids and anticonvulsants
• Dose expansion cohort (B): no prior chemotherapy is allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Dose escalation cohorts	Drug: DSTP3086S; DSTP3086S administered intravenously; Drug: DSTP3086S; Escalating intravenous dose
Experimental: B; Dose expansion cohorts	Drug: DSTP3086S; DSTP3086S administered intravenously; Drug: DSTP3086S; Escalating intravenous dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and nature of dose-limiting toxicities (DLTs)	Days 1-21

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration-time curve	Up to 1 year
Maximum and minimum concentrations	Up to 1 year
Clearance	Up to 1 year
Half-life	Up to 1 year
Volume of distribution	Up to 1 year

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Bernard Fine, M.D., Genentech, Inc.

Publications and helpful links

General Publications

• Martiniova L, Zielinski RJ, Lin M, DePalatis L, Ravizzini GC. The Role of Radiolabeled Monoclonal Antibodies in Cancer Imaging and ADC Treatment. Cancer J. 2022 Nov-Dec 01;28(6):446-453. doi: 10.1097/PPO.0000000000000625.
• Danila DC, Szmulewitz RZ, Vaishampayan U, Higano CS, Baron AD, Gilbert HN, Brunstein F, Milojic-Blair M, Wang B, Kabbarah O, Mamounas M, Fine BM, Maslyar DJ, Ungewickell A, Scher HI. Phase I Study of DSTP3086S, an Antibody-Drug Conjugate Targeting Six-Transmembrane Epithelial Antigen of Prostate 1, in Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2019 Dec 20;37(36):3518-3527. doi: 10.1200/JCO.19.00646. Epub 2019 Nov 5.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: January 21, 2011
• First Submitted That Met QC Criteria: January 24, 2011
• First Posted (Estimate): January 26, 2011

Study Record Updates

• Last Update Posted (Estimate): October 4, 2016
• Last Update Submitted That Met QC Criteria: October 3, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: DST4964g; GO00768 (Other Identifier: Hoffmann-La Roche)