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Trial record 1 of 1 for:    es414
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Study of MOR209/ES414 in Metastatic Castration-Resistant Prostate Cancer

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Aptevo Therapeutics
Sponsor:
Collaborator:
MorphoSys AG
Information provided by (Responsible Party):
Aptevo Therapeutics
ClinicalTrials.gov Identifier:
NCT02262910
First received: September 26, 2014
Last updated: June 22, 2017
Last verified: June 2017
  Purpose

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 MOR209/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 MOR209/ES414.

The primary objective of Stage 2 of the study is to evaluate the clinical activity of MOR209/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 MOR209/ES414.


Condition Intervention Phase
Prostate Cancer Biological: MOR209/ES414 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of MOR209/ES414 in Patients Wtih Metastatic Castration-Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Aptevo Therapeutics:

Primary Outcome Measures:
  • Maximum Tolerated Dose of MOR209/ES414 [ Time Frame: during first 28 days of treatment ]
    Identify the maximum tolerated dose in dose-escalation stage (Stage 1) by assessment of dose-limiting toxicities


Secondary Outcome Measures:
  • Safety Profile of MOR209/ES414 [ Time Frame: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment ]
    The safety profile of ES414 will be assessed by monitoring incidence and severity of adverse events

  • Maximum Serum Drug Concentration (Cmax) [ Time Frame: 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 ]
    Blood samples will be obtained from all patients for determination of the maximum serum concentration of MOR209/ES414.

  • Area under the concentration versus time curve (AUC) [ Time Frame: 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 ]
    Blood samples will be obtained from all patients for determination of the AUC of MOR209/ES414.

  • Elimination half-life (T1/2) [ Time Frame: 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 ]
    Blood samples will be obtained from all patients for determination of the T1/2 of MOR209/ES414.

  • Immune-Related Response Criteria (irRC) [ Time Frame: Baseline and 6 months ]
    Investigator measurements of target lesions

  • Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: Baseline and 6 months ]
    Investigator measurements of target lesions

  • Pharmacodynamics of MOR209/ES414 [ Time Frame: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment ]
    Blood samples will be collected from all patients and evaluated by flow cytometry for changes in lymphocytes

  • PSA Response [ Time Frame: Baseline and 6 months ]
    Blood samples will be collected from all patients and tested for PSA

  • Circulating Tumor Cells [ Time Frame: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment ]
    Blood samples will be collected from all patients and evaluated for the number of circulating tumor cells

  • Immunogenicity of MOR209/ES414 [ Time Frame: Patients will be followed for the duration of treatment, an expected average of 6 months, and for 8 weeks following last treatment ]
    Blood samples will be collected from all patients and tested for antibody formation to ES414.


Estimated Enrollment: 130
Study Start Date: January 2015
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MOR209/ES414
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 MOR209/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 MOR209/ES414 as a continuous IV infusion for 6 months until disease progression, intolerable toxicity occurs, or the patient withdraws consent.
Biological: MOR209/ES414
MOR209/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).

Detailed Description:

Stage 1 - Dose Escalation: The dose escalation stage of the study will test weekly doses of 0.2 mcg/kg to 300 mcg/kg over 9 dose levels (cohorts). Cohorts 1 to 3 consist of single patients and Cohorts 4 - 9 will consist of a minimum of 3 patients; an additional 3 patients may be added to the cohort if adverse events possibly related to MOR209/ES414 or dose-limiting toxicities (DLT) occur. The next dose cohort will only enroll after the patient(s) in the current dose cohort have completed the first cycle of dosing (4 weeks) with no significant adverse events or DLTs. Six patients will be enrolled at the maximum tolerated dose (MTD) and this dose will be used for Stage 2.

Stage 2 - Expansion: The continuous intravenous infusion MTD dose regimen will be further examined in 2 expansion cohorts; the first cohort are patients that have received prior chemotherapy, such as docetaxel for mCRPC, and the second cohort are those that have not received prior chemotherapy for mCRPC. Serum samples will be collected for serial PK assessment for MOR/209ES414 drug levels and antibody formation. Response will be assessed every 2 months during the first 6 months of treatment and then every 3 months until progression of mCRPC, intolerable side effects, or withdrawal of consent.

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02262910

Contacts
Contact: David Schaaf, MD 206-859-6655 schaafd@apvo.com

Locations
United States, California
University of California Recruiting
San Francisco, California, United States, 94143
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
United States, Washington
University of Washington/Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Australia, Victoria
Peter MacCallum Cancer Centre Recruiting
East Melbourne, Victoria, Australia, 3002
The Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia, 3050
Sponsors and Collaborators
Aptevo Therapeutics
MorphoSys AG
Investigators
Study Director: Scott C Stromatt, MD Aptevo Therapeutics
  More Information

Responsible Party: Aptevo Therapeutics
ClinicalTrials.gov Identifier: NCT02262910     History of Changes
Other Study ID Numbers: 401
Study First Received: September 26, 2014
Last Updated: June 22, 2017

Keywords provided by Aptevo Therapeutics:
metastatic castration-resistant prostate cancer
CRPC

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on August 18, 2017