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Safety, Tolerability, Pharmacokinetics, and Efficacy of Acapatamab in Subjects With 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: NCT03792841
Recruitment Status : Active, not recruiting
First Posted : January 3, 2019
Last Update Posted : December 8, 2022
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Description
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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).

Condition or disease Intervention/treatment Phase
Metastatic Castration-resistant Prostate Cancer Prostate Cancer Drug: acapatamab Drug: Pembrolizumab Drug: Etanercept Drug: Cytochrome P450 (CYP) Cocktail Phase 1

Detailed Description:
This is a phase I, first-in-human study to evaluate the safety and tolerability of acapatamab; a half-life extended (HLE) bispecific T-cell engager (BiTE®) construct, alone and in combination with pembrolizumab, etanercept prophylaxis and cytochrome P450 (CYP) phenotyping cocktail in subjects with metastatic castration-resistant prostate cancer.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 212 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : February 5, 2019
Estimated Primary Completion Date : May 16, 2025
Estimated Study Completion Date : May 16, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: acapatamab
Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
Other Name: PSMA Targeted Therapy
Experimental: Part 1 Dose-expansion: acapatamab treatment
Part 1 dose-expansion: acapatamab is administered intravenously at the MTD/RP2D.
 Drug: acapatamab
Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
Other Name: PSMA Targeted Therapy
Experimental: Part 2: acapatamab + Pembrolizumab
Part 2: acapatamab is administered intravenously at the MTD/RP2D. Pembrolizumab will be administered intravenously.
 Drug: acapatamab
Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
Other Name: PSMA Targeted Therapy

Drug: Pembrolizumab
Combined with acapatamab for investigational treatment of mCRPC
Other Name: PD-1 inhibitor
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.
 Drug: acapatamab
Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
Other Name: PSMA Targeted Therapy

Drug: Etanercept
Prophylaxis for acapatamab-related cytokine release syndrome.
Other Name: TNF-alpha inhibitor
Experimental: Part 4: acapatamab 24 Hour Monitoring
Part 4: acapatamab is administered intravenously at RP2D/MTD with 24-hour monitoring.
 Drug: acapatamab
Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
Other Name: PSMA Targeted Therapy
Experimental: Part 5: acapatamab Outpatient Cohort
Part 5: acapatamab is administered intravenously at RP2D/MTD in an outpatient setting with 8-hour monitoring.
 Drug: acapatamab
Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
Other Name: PSMA Targeted Therapy
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.
 Drug: acapatamab
Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
Other Name: PSMA Targeted Therapy

Drug: Cytochrome P450 (CYP) Cocktail
Evaluate the effect of co-administration of multiple dosing of acapatamab on plasma
Other Name: Cooperstown 5+1 CYP phenotyping cocktail


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants with dose-limiting toxicity [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  2. Number of participants with treatment-emergent adverse events [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  3. Number of participants with treatment-related adverse events [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  4. Number of participants with clinically significant changes in vital signs [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  5. Number of participants with clinically significant changes in electrocardiogram (ECG) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  6. Number of participants with clinically significant changes in clinical laboratory tests [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study


Secondary Outcome Measures :
  1. Maximum serum concentration (Cmax) of acapatamab [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  2. Minimum serum concentration (Cmin) of acapatamab [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  3. Area under the concentration-time curve (AUC) over the dosing interval of acapatamab [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  4. Accumulation ratio of acapatamab [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  5. Half-life of acapatamab [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  6. Objective response (OR) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  7. Prostate-specific antigen (PSA) response [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  8. Duration of response (DOR) (radiographic and PSA) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  9. 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 [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 only.

  10. Percentage of participants experiencing a response based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) response evaluations [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 only.

  11. Change in time to progression (radiographic and PSA) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  12. Progression-free survival (PFS) (radiographic and PSA) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study.

  13. 1, 2 and 3-year overall survival (OS) [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  14. Percentage of participants experiencing circulating tumor cells (CTC) response [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study. CTC response defined as CTC0 (reduction of CTCs > 0 to 0) or CTC conversion (≥ 5 CTCs/7.5 mL blood to ≤ 4 CTCs/7.5 mL blood)

  15. Other PCWG3-recommended endpoints - time to symptomatic skeletal events [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  16. Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH] levels [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  17. Other PCWG3-recommended endpoints - hemoglobin levels [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  18. Other PCWG3-recommended endpoints - neutrophil-to-lymphocyte ratio [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  19. Other PCWG3-recommended endpoints - urine N-telopeptide levels [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  20. Other PCWG3-recommended endpoints - alkaline phosphatase [total, bone] levels [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

  21. Maximum serum concentration (Cmax) of acapatamab when administered with CYP enzymes [ Time Frame: Up to 3 years ]
    Part 6 only.

  22. Area under the concentration-time curve over a 24-hour period (AUC24) of acapatamab when administered with CYP enzymes [ Time Frame: Up to 3 years ]
    Part 6 only.

  23. Half-life of acapatamab when administered with CYP enzymes [ Time Frame: Up to 3 years ]
    Part 6 only.


Eligibility Criteria
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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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

All Parts

Inclusion Criteria:

  • 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

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
Contacts and Locations
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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): NCT03792841


Locations
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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
More Information
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Additional Information:

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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03792841    
Other Study ID Numbers: 20180101
First Posted: January 3, 2019    Key Record Dates
Last Update Posted: December 8, 2022
Last Verified: December 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 (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.
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, 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.
URL: https://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
HLE-BiTE®
mCRPC
Metastatic Castration-resistant Prostate Cancer
Prostate cancer
PSMA
BiTE®
 Bispecific T-Cell engager
Immunotherapy
Immuno-oncology
Immunooncology
Solid tumor
PSMA Targeted Therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Etanercept
Pembrolizumab
Immune Checkpoint Inhibitors
Antineoplastic Agents, Immunological
 Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors