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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02262910




Registration number
NCT02262910
Ethics application status
Date submitted
26/09/2014
Date registered
13/10/2014
Date last updated
28/08/2019

Titles & IDs
Public title
Study of ES414 in Metastatic Castration-Resistant Prostate Cancer
Scientific title
A Phase 1 Study of ES414 in Patients Wtih Metastatic Castration-Resistant Prostate Cancer
Secondary ID [1] 0 0
401
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - ES414

Experimental: 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 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.


Other interventions: ES414
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).

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose of ES414 - Identify the maximum tolerated dose in dose-escalation stage (Stage 1) by assessment of dose-limiting toxicities
Timepoint [1] 0 0
during first 28 days of treatment
Secondary outcome [1] 0 0
Safety Profile of ES414 - The safety profile of ES414 will be assessed by monitoring incidence and severity of adverse events
Timepoint [1] 0 0
Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
Secondary outcome [2] 0 0
Maximum Serum Drug Concentration (Cmax) - Blood samples will be obtained from all patients for determination of the maximum serum concentration of ES414.
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Area under the concentration versus time curve (AUC) - Blood samples will be obtained from all patients for determination of the AUC of ES414.
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Elimination half-life (T1/2) - Blood samples will be obtained from all patients for determination of the T1/2 of ES414.
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Immune-Related Response Criteria (irRC) - Investigator measurements of target lesions
Timepoint [5] 0 0
Baseline and 6 months
Secondary outcome [6] 0 0
Response Evaluation Criteria in Solid Tumors (RECIST 1.1) - Investigator measurements of target lesions
Timepoint [6] 0 0
Baseline and 6 months
Secondary outcome [7] 0 0
Pharmacodynamics of ES414 - Blood samples will be collected from all patients and evaluated by flow cytometry for changes in lymphocytes
Timepoint [7] 0 0
Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
Secondary outcome [8] 0 0
PSA Response - Blood samples will be collected from all patients and tested for PSA
Timepoint [8] 0 0
Baseline and 6 months
Secondary outcome [9] 0 0
Circulating Tumor Cells - Blood samples will be collected from all patients and evaluated for the number of circulating tumor cells
Timepoint [9] 0 0
Patients will be followed for the duration of treatment, an expected average of 6 months, and for 28 days following last treatment
Secondary outcome [10] 0 0
Immunogenicity of ES414 - Blood samples will be collected from all patients and tested for antibody formation to ES414.
Timepoint [10] 0 0
Patients will be followed for the duration of treatment, an expected average of 6 months, and for 8 weeks following last treatment

Eligibility
Key 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
Minimum age
No limit
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St. Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Aptevo Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02262910
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Scott C Stromatt, MD
Address 0 0
Aptevo Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications