Safety, Tolerability, Pharmacokinetics, and Efficacy of Acapatamab in Subjects With mCRPC

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03792841
• Other study ID #: 20180101
• Status: Completed
• Phase: Phase 1
• Start date: February 5, 2019
• Est. completion date: July 3, 2023

Study information

• Verified date: October 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 212
• Est. completion date: July 3, 2023
• Est. primary completion date: July 3, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• acapatamab
Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer
• Pembrolizumab
Combined with acapatamab for investigational treatment of mCRPC
• Etanercept
Prophylaxis for acapatamab-related cytokine release syndrome.
• Cytochrome P450 (CYP) Cocktail
Evaluate the effect of co-administration of multiple dosing of acapatamab on plasma

Locations

Country	Name	City	State
Australia	Chris OBrien Lifehouse	Camperdown	New South Wales
Australia	Peter MacCallum Cancer Centre	Parkville	Victoria
Australia	Scientia Clinical Research Ltd	Randwick	New South Wales
Austria	Ordensklinikum Linz Elisabethinen	Linz
Austria	Landeskrankenhaus Salzburg	Salzburg
Austria	Krankenhaus der Barmherzigen Brueder Wien	Wien
Austria	Universitaetsklinikum Allgemeines Krankenhaus Wien	Wien
Belgium	Universite Catholique de Louvain Cliniques Universitaires Saint Luc	Bruxelles
Belgium	Universitair Ziekenhuis Gent	Gent
Canada	BC Cancer Vancouver	Vancouver	British Columbia
France	Institut Gustave Roussy	Villejuif Cedex
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba
Japan	Yokohama City University Medical Center	Yokohama-shi	Kanagawa
Netherlands	Erasmus Medisch Centrum	Rotterdam
Singapore	National Cancer Centre Singapore	Singapore
Singapore	National University Hospital	Singapore
Taiwan	Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation	Taoyuan
United States	Emory University	Atlanta	Georgia
United States	El Camino Hospital	Campbell	California
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	City of Hope National Medical Center	Duarte	California
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	City of Hope at Long Beach Elm	Long Beach	California
United States	University of California Los Angeles	Los Angeles	California
United States	Tulane Medical Center	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Washington University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  France,  Japan,  Netherlands,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with dose-limiting toxicity	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Primary	Number of participants with treatment-emergent adverse events	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Primary	Number of participants with treatment-related adverse events	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Primary	Number of participants with clinically significant changes in vital signs	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Primary	Number of participants with clinically significant changes in electrocardiogram (ECG)	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Primary	Number of participants with clinically significant changes in clinical laboratory tests	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Maximum serum concentration (Cmax) of acapatamab	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Minimum serum concentration (Cmin) of acapatamab	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Area under the concentration-time curve (AUC) over the dosing interval of acapatamab	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Accumulation ratio of acapatamab	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Half-life of acapatamab	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Objective response (OR)	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Prostate-specific antigen (PSA) response	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Duration of response (DOR) (radiographic and PSA)	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	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	Parts 1, 2 and 3 only.	Up to 3 years
Secondary	Percentage of participants experiencing a response based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) response evaluations	Parts 1, 2 and 3 only.	Up to 3 years
Secondary	Change in time to progression (radiographic and PSA)	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Progression-free survival (PFS) (radiographic and PSA)	Parts 1, 2, 3, 4, 5, and 6 of the study.	Up to 3 years
Secondary	1, 2 and 3-year overall survival (OS)	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Percentage of participants experiencing circulating tumor cells (CTC) response	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)	Up to 3 years
Secondary	Other PCWG3-recommended endpoints - time to symptomatic skeletal events	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH] levels	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Other PCWG3-recommended endpoints - hemoglobin levels	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Other PCWG3-recommended endpoints - neutrophil-to-lymphocyte ratio	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Other PCWG3-recommended endpoints - urine N-telopeptide levels	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Other PCWG3-recommended endpoints - alkaline phosphatase [total, bone] levels	Parts 1, 2, 3, 4, 5, and 6 of the study	Up to 3 years
Secondary	Maximum serum concentration (Cmax) of acapatamab when administered with CYP enzymes	Part 6 only.	Up to 3 years
Secondary	Area under the concentration-time curve over a 24-hour period (AUC24) of acapatamab when administered with CYP enzymes	Part 6 only.	Up to 3 years
Secondary	Half-life of acapatamab when administered with CYP enzymes	Part 6 only.	Up to 3 years

External Links

•   AmgenTrials clinical trials website