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Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04631601
Recruitment Status : Active, not recruiting
First Posted : November 17, 2020
Last Update Posted : June 22, 2022
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
This is a master protocol designed to evaluate the safety and efficacy of investigational therapies in participants with metastatic castration-resistant prostate cancer (mCRPC).

Condition or disease Intervention/treatment Phase
Metastatic Castration-resistant Prostate Cancer Drug: Acapatamab Drug: Enzalutamide Drug: Abiraterone Drug: AMG 404 Phase 1 Phase 2

Detailed Description:
This is a master protocol designed to evaluate the safety, tolerability, and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and efficacy of Acapatamab, in combination with enzalutamide, abiraterone, or the PD1 inhibitor AMG 404, AMG 404 monotherapy, as well as Acapatamab monotherapy, in participants with metastatic castration-resistant prostate cancer (mCRPC).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 136 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)
Actual Study Start Date : January 15, 2021
Estimated Primary Completion Date : January 27, 2023
Estimated Study Completion Date : July 28, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Acapatamab and Enzalutamide: Dose Exploration
The dose-exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with enzalutamide.
Drug: Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: Enzalutamide
Enzalutamide will be administered orally.
Other Name: Androgen receptor inhibitor

Experimental: Acapatamab and Enzalutamide: Dose Expansion
Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with enzalutamide.
Drug: Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: Enzalutamide
Enzalutamide will be administered orally.
Other Name: Androgen receptor inhibitor

Experimental: Acapatamab and Abiraterone: Dose Exploration
The dose exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with abiraterone.
Drug: Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: Abiraterone
Abiraterone will be administered orally.
Other Name: Cytochrome P450 (CYP)17 inhibitor

Experimental: Acapatamab and Abiraterone: Dose Expansion
Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with abiraterone.
Drug: Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: Abiraterone
Abiraterone will be administered orally.
Other Name: Cytochrome P450 (CYP)17 inhibitor

Experimental: Acapatamab and AMG 404: Dose Exploration
The dose-exploration part of the study will estimate the MTD/RP2D of Acapatamab in combination with AMG 404.
Drug: Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: AMG 404
AMG 404 will be administered as an intravenous (IV) infusion.
Other Name: PD-1 inhibitor

Experimental: Acapatamab and AMG 404: Dose Expansion
Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with AMG 404.
Drug: Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: AMG 404
AMG 404 will be administered as an intravenous (IV) infusion.
Other Name: PD-1 inhibitor

Active Comparator: AMG 404 Monotherapy
AMG 404 monotherapy is being conducted to evaluate the preliminary anti-tumor activity of PD-1 inhibition in the mCRPC population.
Drug: AMG 404
AMG 404 will be administered as an intravenous (IV) infusion.
Other Name: PD-1 inhibitor

Experimental: Acapatamab and Enzalutamide: Dose Expansion Asia Cohort
Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with enzalutamide for subjects in Asia.
Drug: Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: Enzalutamide
Enzalutamide will be administered orally.
Other Name: Androgen receptor inhibitor

Experimental: Acapatamab and Abiraterone: Dose Expansion Asia Cohort
Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with abiraterone for subjects in Asia.
Drug: Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: Abiraterone
Abiraterone will be administered orally.
Other Name: Cytochrome P450 (CYP)17 inhibitor

Experimental: Acapatamab and AMG 404: Dose Expansion Asia Cohort
Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with AMG 404 for subjects in Asia.
Drug: Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: AMG 404
AMG 404 will be administered as an intravenous (IV) infusion.
Other Name: PD-1 inhibitor

Experimental: Acapatamab Monotherapy
Acapatamab monotherapy is being conducted to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and efficacy of Acapatamab in subjects with mCRPC.
Drug: Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy




Primary Outcome Measures :
  1. Dose exploration only: Number of participants who experience dose limiting toxicities (DLTs) [ Time Frame: Up to 3 years ]

    The analysis of all endpoints, unless noted otherwise, will be conducted on the Safety Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of Acapatamab. The analysis of dose-limiting toxicity (DLT) will be conducted on the DLT Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of Acapatamab with an evaluable DLT endpoint. If a single subject experiences more than 1 DLT it will be counted as 1.

    The DLT endpoint is evaluable if either:

    1) the subject experiences a DLT; or 2) the subject does not experience a DLT after receiving all planned doses within the 28-day DLT window in cycle 1.


  2. Number of participants who experience one or more treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 3 years ]
  3. Number of participants who experience one or more treatment-related adverse events [ Time Frame: Up to 3 years ]
  4. Number of participants who experience a clinically significant change in vital signs [ Time Frame: Up to 3 years ]
  5. Number of participants who experience a clinically significant change in clinical laboratory tests [ Time Frame: Up to 3 years ]

Secondary Outcome Measures :
  1. Objective response rate per response evaluation criteria in solid tumors (RECIST) 1.1 with prostate cancer working group 3 (PCWG3) modifications [ Time Frame: Up to 3 years ]
  2. Number of participants who experience circulating tumor cell (CTC) response [ Time Frame: Up to 3 years ]
  3. Number of participants who experience prostate-specific antigen (PSA) response rate [ Time Frame: Up to 3 years ]
  4. Duration of response [ Time Frame: Up to 3 years ]
  5. Overall survival (OS) [ Time Frame: Up to 3 years ]
  6. Progression-free survival [ Time Frame: Up to 3 years ]
  7. Time to progression [ Time Frame: Up to 3 years ]
  8. Time to subsequent therapy [ Time Frame: Up to 3 years ]
  9. Maximum plasma concentration (Cmax) [ Time Frame: Up to 3 years ]
  10. Minimum plasma concentration (Cmin) [ Time Frame: Up to 3 years ]
  11. Area under the concentration-time curve (AUC) [ Time Frame: Up to 3 years ]
  12. Accumulation ratio based on area under the concentration-time curve (AUC) [ Time Frame: Up to 3 years ]
  13. Half-life (t1/2) [ Time Frame: Up to 3 years ]
  14. Change from baseline in prostate-specific membrane antigen (PSMA)-positive tumor burden assessed using gallium (GA) 68-labelled PSMA-11 positron emission tomography/computed tomography (PET/CT) [ Time Frame: Baseline up to 3 years ]
  15. Change from baseline in prostate-specific membrane antigen (PSMA)-negative disease burden assessed using 18F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) [ Time Frame: Baseline to 3 years ]
  16. Time to symptomatic skeletal events [ Time Frame: Up to 3 years ]
  17. Concentration of alkaline phosphatase [ Time Frame: Up to 3 years ]
  18. Concentration of lactate dehydrogenase (LDH) [ Time Frame: Up to 3 years ]
  19. Concentration of hemoglobin [ Time Frame: Up to 3 years ]
  20. Neutrophil-to-lymphocyte ratio [ Time Frame: Up to 3 years ]
  21. Concentration of N-telopeptide in the urine [ Time Frame: Up to 3 years ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

All parts

Inclusion Criteria:

  • ≥ 18 years of age (or legal adult age within country)
  • Subject has provided informed consent prior to initiation of any study-specific activities/procedures
  • Subjects with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate
  • Subjects should have undergone bilateral orchiectomy or should be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist (testosterone ≤ 50 ng/dL (or 1.7 nmol/L))

Exclusion Criteria:

  • Central nervous system (CNS) metastases or leptomeningeal disease
  • History or presence of clinically relevant CNS pathology
  • Confirmed history or current autoimmune disease or other diseases requiring permanent immunosuppressive therapy
  • Myocardial infarction, uncontrolled hypertension, unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months
  • Prior treatment with a taxane for mCRPC
  • Major surgery and/or Radiation within 4 weeks
  • History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless agreed upon with medical monitor and meeting the following criteria:

    • Negative test for SARS-CoV-2 RNA by real time polymerase chain reaction (RT-PCR) within 72 hours of first dose of Acapatamab (or AMG 404 in Part 3)
    • No acute symptoms of COVID-19 disease within 10 days prior to first dose of Acapatamab (or AMG 404 in Part 3) (counted from day of positive test for asymptomatic subjects)

Prior/Concurrent Clinical Study Experience

  • Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded with the exception of investigational scans.

Subprotocol A only:

Inclusion criteria

• Subjects planning to receive enzalutamide for the first time for mCRPC

Exclusion criteria

  • Use of strong CYP2C8 inhibitors or strong CYP3A4 inducers
  • Use of narrow therapeutic index drugs that are substrates of CYP3A4, CYP2C9 or CYP2C19

Subprotocol B only:

Inclusion criteria

  • Subjects planning to receive abiraterone for the first time for mCRPC Exclusion criteria
  • Baseline moderate and severe hepatic impairment (Child-Pugh Class B and C)
  • Presence of uncontrolled hypertension, hypokalemia, or fluid retention
  • History or presence of adrenocortical insufficiency
  • Use of concomitant medications that are sensitive substrates for CYP2D6 with a narrow therapeutic index
  • Use of strong CYP3A4 inducers

Subprotocol C only:

Inclusion criteria

  • Subjects who are refractory to a novel antiandrogen therapy. Subjects must be ineligible for or refuse taxane therapy.
  • 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, and/or appearance of 2 or more new lesions in bone scan Exclusion criteria
  • History or evidence of interstitial lung disease or active, non-infectious pneumonitis
  • 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 dose

Subprotocol D only:

Inclusion criteria

  • Subjects may have had novel hormonal therapies (NHT; eg, abiraterone, enzalutamide, apalutamide, or darolutamide) for prostate cancer, but no more than 1 NHT for metastatic prostate cancer
  • Ineligible for or refuse taxane therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04631601


Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of California at Irvine Medical Center
Orange, California, United States, 92868
University of California San Francisco Mission Bay Campus
San Francisco, California, United States, 94158
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Kentucky
Norton Cancer Institute
Louisville, Kentucky, United States, 40207
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Australia, New South Wales
St Vincents Hospital Sydney
Darlinghurst, New South Wales, Australia, 2010
Denmark
Rigshospitalet
Kobenhavn O, Denmark, 2100
Spain
Clinica Universidad de Navarra
Pamplona, Navarra, Spain, 31008
Sweden
Skanes universitetssjukhus
Lund, Sweden, 221 85
Karolinska Universitetssjukhuset Solna
Stockholm, Sweden, 171 76
Akademiska sjukhuset
Uppsala, Sweden, 75185
United Kingdom
Royal Marsden Hospital
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT04631601    
Other Study ID Numbers: 20190505
2020-001305-23 ( EudraCT Number )
First Posted: November 17, 2020    Key Record Dates
Last Update Posted: June 22, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: 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 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.
Access Criteria: 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. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. 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.
URL: http://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Acapatamab
HALF-LIFE EXTENDED (HLE) BITE
mCRPC
Metastatic Castration-resistant Prostate Cancer
68
Gallium (68Ga)-prostate-specific membrane
antigen (PSMA)-11 positron emission
tomography(PET)/computed tomography (CT)
and
18
F-fluorodeoxyglucose (FDG) PET/CT
based response evaluation
Bispecific T cell Engager
BITE
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Immune Checkpoint Inhibitors
Androgens
Androgen Receptor Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Androgen Antagonists
Hormone Antagonists