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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03792841




Registration number
NCT03792841
Ethics application status
Date submitted
2/01/2019
Date registered
3/01/2019

Titles & IDs
Public title
Safety, Tolerability, Pharmacokinetics, and Efficacy of Acapatamab in Subjects With mCRPC
Scientific title
A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Prostate Specific Membrane Antigen Half-life Extended Bispecific T-cell Engager Acapatamab in Subjects With Metastatic Castration-resistant Prostate Cancer
Secondary ID [1] 0 0
20180101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration-resistant Prostate Cancer 0 0
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - acapatamab
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Etanercept
Treatment: Drugs - Cytochrome P450 (CYP) Cocktail

Experimental: Part 1 Dose-exploration: acapatamab treatment - Part 1 dose-exploration: acapatamab is administered intravenously. The dose-exploration phase of the study will estimate the MTD of acapatamab. RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an MTD.

Experimental: Part 1 Dose-expansion: acapatamab treatment - Part 1 dose-expansion: acapatamab is administered intravenously at the MTD/RP2D.

Experimental: Part 2: acapatamab + Pembrolizumab - Part 2: acapatamab is administered intravenously at the MTD/RP2D. Pembrolizumab will be administered intravenously.

Experimental: Part 3: acapatamab + Etanercept Prophylaxis - Part 3: acapatamab is administered intravenously at RP2D/MTD levels. Etanercept will be administered subcutaneously in cycle 1 only.

Experimental: Part 4: acapatamab 24 Hour Monitoring - Part 4: acapatamab is administered intravenously at RP2D/MTD with 24-hour monitoring.

Experimental: Part 5: acapatamab Outpatient Cohort - Part 5: acapatamab is administered intravenously at RP2D/MTD in an outpatient setting with 8-hour monitoring.

Experimental: Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug Interaction - Part 6: acapatamab is administered intravenously at RP2D/MTD. A CYP phenotyping cocktail will be administered orally.


Treatment: Drugs: acapatamab
Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer

Treatment: Drugs: Pembrolizumab
Combined with acapatamab for investigational treatment of mCRPC

Treatment: Drugs: Etanercept
Prophylaxis for acapatamab-related cytokine release syndrome.

Treatment: Drugs: Cytochrome P450 (CYP) Cocktail
Evaluate the effect of co-administration of multiple dosing of acapatamab on plasma
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with dose-limiting toxicity
Timepoint [1] 0 0
Up to 3 years
Primary outcome [2] 0 0
Number of participants with treatment-emergent adverse events
Timepoint [2] 0 0
Up to 3 years
Primary outcome [3] 0 0
Number of participants with treatment-related adverse events
Timepoint [3] 0 0
Up to 3 years
Primary outcome [4] 0 0
Number of participants with clinically significant changes in vital signs
Timepoint [4] 0 0
Up to 3 years
Primary outcome [5] 0 0
Number of participants with clinically significant changes in electrocardiogram (ECG)
Timepoint [5] 0 0
Up to 3 years
Primary outcome [6] 0 0
Number of participants with clinically significant changes in clinical laboratory tests
Timepoint [6] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Maximum serum concentration (Cmax) of acapatamab
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Minimum serum concentration (Cmin) of acapatamab
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
Area under the concentration-time curve (AUC) over the dosing interval of acapatamab
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Accumulation ratio of acapatamab
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
Half-life of acapatamab
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Objective response (OR)
Timepoint [6] 0 0
Up to 3 years
Secondary outcome [7] 0 0
Prostate-specific antigen (PSA) response
Timepoint [7] 0 0
Up to 3 years
Secondary outcome [8] 0 0
Duration of response (DOR) (radiographic and PSA)
Timepoint [8] 0 0
Up to 3 years
Secondary outcome [9] 0 0
Percentage of participants experiencing a response based on 68Gallium (68Ga)-prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (CT) response evaluations
Timepoint [9] 0 0
Up to 3 years
Secondary outcome [10] 0 0
Percentage of participants experiencing a response based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) response evaluations
Timepoint [10] 0 0
Up to 3 years
Secondary outcome [11] 0 0
Change in time to progression (radiographic and PSA)
Timepoint [11] 0 0
Up to 3 years
Secondary outcome [12] 0 0
Progression-free survival (PFS) (radiographic and PSA)
Timepoint [12] 0 0
Up to 3 years
Secondary outcome [13] 0 0
1, 2 and 3-year overall survival (OS)
Timepoint [13] 0 0
Up to 3 years
Secondary outcome [14] 0 0
Percentage of participants experiencing circulating tumor cells (CTC) response
Timepoint [14] 0 0
Up to 3 years
Secondary outcome [15] 0 0
Other PCWG3-recommended endpoints - time to symptomatic skeletal events
Timepoint [15] 0 0
Up to 3 years
Secondary outcome [16] 0 0
Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH] levels
Timepoint [16] 0 0
Up to 3 years
Secondary outcome [17] 0 0
Other PCWG3-recommended endpoints - hemoglobin levels
Timepoint [17] 0 0
Up to 3 years
Secondary outcome [18] 0 0
Other PCWG3-recommended endpoints - neutrophil-to-lymphocyte ratio
Timepoint [18] 0 0
Up to 3 years
Secondary outcome [19] 0 0
Other PCWG3-recommended endpoints - urine N-telopeptide levels
Timepoint [19] 0 0
Up to 3 years
Secondary outcome [20] 0 0
Other PCWG3-recommended endpoints - alkaline phosphatase [total, bone] levels
Timepoint [20] 0 0
Up to 3 years
Secondary outcome [21] 0 0
Maximum serum concentration (Cmax) of acapatamab when administered with CYP enzymes
Timepoint [21] 0 0
Up to 3 years
Secondary outcome [22] 0 0
Area under the concentration-time curve over a 24-hour period (AUC24) of acapatamab when administered with CYP enzymes
Timepoint [22] 0 0
Up to 3 years
Secondary outcome [23] 0 0
Half-life of acapatamab when administered with CYP enzymes
Timepoint [23] 0 0
Up to 3 years

Eligibility
Key inclusion criteria
All Parts



* Subject has provided informed consent prior to initiation of any study specific activities/procedures
* Subjects with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (abiraterone, enzalutamide, and/or apalutamide) and have failed at least 1 (but not more than 2) taxane regimens (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Progression on novel antiandrogen therapy may have occurred in the non-metastatic CRPC setting
* Subjects must have undergone bilateral orchiectomy or must be on continuous ADT with a gonadotropin releasing hormone (GnRH) agonist or antagonist
* Total serum testosterone </= 50 ng/dL or 1.7 nmol/L
* Evidence of progressive disease, defined as 1 or more PCWG3 criteria:
* PSA level >/= 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart
* nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications
* appearance of 2 or more new lesions in bone scan
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
* Life expectancy >/= 6months
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone agonist (LHRH)/GnRH analogue (agonist/antagonist). Subjects on a stable bisophosphonate or denosumab regimen for >/= 30 days prior to randomization are eligible
* Prior PSMA-targeted therapy (subjects on prior therapy may be eligible if discussed with Amgen medical monitor prior to enrollment)
* Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
* Active autoimmune disease or any other diseases requiring immunosuppressive therapy while on study
* Needing chronic systemic corticosteroid therapy (prednisone > 10 mg per day or equivalent) or any other immunosuppressive therapies (including anti-tumor necrosis factor alpha [TNF alpha] therapies) unless stopped 7 days prior to start of first dose
* Myocardial infarction, unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of acapatamab

Part 2 only:

* Subjects on a prior PD-1 or PD-L1 inhibitor who experienced a Grade 3 or higher immune-related adverse event prior to first day of dosing
* History or evidence of interstitial lung disease or active, non-infectious pneumonitis

Part 3 only:

- Evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product

Part 6 only:

Subjects are excluded from this cohort if any of the following additional criteria apply:

* Subjects taking strong OAT3 inhibitors (eg, probenecid) or adjust the dosing to 1 mg PO QD.
* Subjects with latent or active tuberculosis at screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
Other
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
5/02/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/06/2023
Sample size
Target
Accrual to date
Final
212
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Scientia Clinical Research Ltd - Randwick
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
3050 - Parkville
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
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Louisiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Austria
State/province [10] 0 0
Linz
Country [11] 0 0
Austria
State/province [11] 0 0
Salzburg
Country [12] 0 0
Austria
State/province [12] 0 0
Wien
Country [13] 0 0
Belgium
State/province [13] 0 0
Bruxelles
Country [14] 0 0
Belgium
State/province [14] 0 0
Gent
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
France
State/province [16] 0 0
Villejuif Cedex
Country [17] 0 0
Japan
State/province [17] 0 0
Chiba
Country [18] 0 0
Japan
State/province [18] 0 0
Kanagawa
Country [19] 0 0
Netherlands
State/province [19] 0 0
Rotterdam
Country [20] 0 0
Singapore
State/province [20] 0 0
Singapore
Country [21] 0 0
Taiwan
State/province [21] 0 0
Taoyuan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe, or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03792841