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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03792841




Registration number
NCT03792841
Ethics application status
Date submitted
2/01/2019
Date registered
3/01/2019
Date last updated
18/10/2023

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
3/07/2023
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
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, and to determine the maximum
tolerated dose (MTD) or recommended phase 2 dose (RP2D).
Trial website
https://clinicaltrials.gov/ct2/show/NCT03792841
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03792841