Study of ES414 in Metastatic Castration-Resistant Prostate Cancer

NCT02262910 | Completed Phase 1

• 1 other identifier: 401
• Study Type: interventional
• Target: 35
• Locations: 2 countries
• Sites: 7

Brief Summary

The study will be conducted in 2 Stages. The primary objective of Stage 1 of the study is to identify the maximum tolerated dose (MTD) of ES414 administered intravenously to patients with mCRPC. Secondary objectives are to evaluate the tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, cytokine response, and clinical activity of ES414. The primary objective of Stage 2 of the study is to evaluate the clinical activity of ES414 in patients that have or have not received prior chemotherapy. Secondary objectives are to further characterize the safety profile, PK, PD, and immunogenicity of ES414.

Conditions

Prostate Cancer

Keywords

metastatic castration-resistant prostate cancer; CRPC

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of ES414

  Identify the maximum tolerated dose in dose-escalation stage (Stage 1) by assessment of dose-limiting toxicities

  during first 28 days of treatment

Secondary Outcomes (10)

• Safety Profile of ES414

  Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment

• Maximum Serum Drug Concentration (Cmax)

  Pre- and post-infusion at least weekly during first 28-day cycle, and on Days 1 and 15 of subsequent cycles for an expected duration of 6 months, and for up to 8 weeks following last treatment

• Area under the concentration versus time curve (AUC)

  Pre- and post-infusion at least weekly during first 28-day cycle, and on Days 1 and 15 of subsequent cycles for an expected duration of 6 months, and for up to 8 weeks following last treatment

• Elimination half-life (T1/2)

  Pre- and post-infusion at least weekly during first 28-day cycle, and on Days 1 and 15 of subsequent cycles for an expected duration of 6 months, and for up to 8 weeks following last treatment

• Immune-Related Response Criteria (irRC)

  Baseline and 6 months

Study Arms (1)

ES414

EXPERIMENTAL

Cohorts 1-3 of the dose escalation stage of the study (Stage 1) will test weekly doses of 0.2 mcg/kg to 2 mcg/kg. Cohorts 4-9 of the dose escalation stage of the study (Stage 1) will test continuous infusion at flat doses of 25 mcg to 300 mcg per day delivered continuously over 24 hours. The maximum tolerated dose from Stage 1 of the study will be further examined in Stage 2. Patients in cohorts 1-3 will receive ES414 weekly via intravenous (IV) infusion during the first three 28-day cycles and then on Day 1 and 15 of each subsequent cycle until disease progression, intolerable toxicity occurs, or the patient withdraws consent. Patients in cohorts 4-9 will receive ES414 as a continuous IV infusion for 6 months until disease progression, intolerable toxicity occurs, or the patient withdraws consent.

Biological: ES414

Interventions

ES414 BIOLOGICAL

ES414 is a novel humanized bispecific antibody which is designed to treat mCRPC by redirecting T-cell cytotoxicity against prostate cancer cells expressing prostate-specific membrane antigen (PSMA).

ES414

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the prostate. No evidence of neuroendocrine differentiation or small cell features.
• Surgically or medically castrated, with testosterone ≤ 50 ng/dL (≤ 1.7 nmol/L).
• Progressive prostate cancer by either serum PSA levels, soft tissue or bone disease as defined by the PCWG2 criteria.
• In Stage 1, patients may or may not have received prior chemotherapy for mCRPC. In Stage 2, patients will be enrolled into two cohorts based on whether or not they have received prior chemotherapy for mCRPC. Any prior chemotherapy must have been completed ≥ 4 weeks prior to administration of ES414. Additionally, in countries where abiraterone or enzalutamide are commercially available, patients in Stage 1 and 2 must have progressed on abiraterone and/or enzalutamide prior to study entry.
• ECOG ≤ 1
• Life expectancy \> 6 months per investigator
• Adequate hematologic, renal, and hepatic parameters

You may not qualify if:

• Any chemotherapy, sipuleucel-T, or investigational drug in prior 4 weeks, or abiraterone or enzalutamide in prior 2 week
• Any radiation therapy in prior 2 weeks
• Any prior therapy targeted against PSMA
• History of seizures
• History of central nervous system metastasis
• History of nephrotic syndrome
• Spot urine total protein:creatinine ratio \>1,000 mg/gm
• Planned palliative procedures for alleviation of bone pain
• Active infection requiring treatment with systemic anti-infectives or major surgery in prior 4 weeks.
• Any prednisone (or equivalent corticosteroids) use within 2 weeks of study entry
• Chronic immunosuppressive therapy
• Known history of HIV, hepatitis B, or hepatitis C infection
• Evidence of severe or uncontrolled systemic diseases
• History of bleeding disorders or thromboembolic events in prior 3 months

Sponsors & Collaborators

• Aptevo Therapeutics: lead

Study Sites (7)

University of California

San Francisco, California, 94143, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Central Texas Veterans Health Care System

Temple, Texas, 76504, United States

Location

University of Washington/Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

St. Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Scott C Stromatt, MD

  Aptevo Therapeutics

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: September 26, 2014
• First Posted: October 13, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: February 18, 2019
• Last Updated: August 28, 2019

Record last verified: 2019-08

Locations

US (4); AU (3)