Clinical trial NCT04631601: Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)
Official title: A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Castration-resistant Prostate Cancer
Keywords: 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
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2020-11-17
Enrollment: 65
Sex: MALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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).

Eligibility 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

Primary outcomes:
measure: Dose exploration only: Number of participants who experience dose limiting toxicities (DLTs)
timeFrame: Up to 3 years
measure: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)
timeFrame: Up to 3 years
measure: Number of participants who experience one or more treatment-related adverse events
timeFrame: Up to 3 years
measure: Number of participants who experience a clinically significant change in vital signs
timeFrame: Up to 3 years
measure: Number of participants who experience a clinically significant change in clinical laboratory tests
timeFrame: Up to 3 years
Secondary outcomes:
measure: Objective response rate per response evaluation criteria in solid tumors (RECIST) 1.1 with prostate cancer working group 3 (PCWG3) modifications
timeFrame: Up to 3 years
measure: Number of participants who experience circulating tumor cell (CTC) response
timeFrame: Up to 3 years
measure: Number of participants who experience prostate-specific antigen (PSA) response rate
timeFrame: Up to 3 years
measure: Duration of response
timeFrame: Up to 3 years
measure: Overall survival (OS)
timeFrame: Up to 3 years
measure: Progression-free survival
timeFrame: Up to 3 years
measure: Time to progression
timeFrame: Up to 3 years
measure: Time to subsequent therapy
timeFrame: Up to 3 years
measure: Maximum plasma concentration (Cmax)
timeFrame: Up to 3 years
measure: Minimum plasma concentration (Cmin)
timeFrame: Up to 3 years
measure: Area under the concentration-time curve (AUC)
timeFrame: Up to 3 years
measure: Accumulation ratio based on area under the concentration-time curve (AUC)
timeFrame: Up to 3 years
measure: Half-life (t1/2)
timeFrame: Up to 3 years
measure: 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)
timeFrame: Baseline up to 3 years
measure: 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)
timeFrame: Baseline to 3 years
measure: Time to symptomatic skeletal events
timeFrame: Up to 3 years
measure: Concentration of alkaline phosphatase
timeFrame: Up to 3 years
measure: Concentration of lactate dehydrogenase (LDH)
timeFrame: Up to 3 years
measure: Concentration of hemoglobin
timeFrame: Up to 3 years
measure: Neutrophil-to-lymphocyte ratio
timeFrame: Up to 3 years
measure: Concentration of N-telopeptide in the urine
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Orange
country: United States
facility: University of California at Irvine Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Mission Bay Campus
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Darlinghurst
country: Australia
facility: St Vincents Hospital Sydney
state: New South Wales
city: Kobenhavn O
country: Denmark
facility: Rigshospitalet
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Lund
country: Sweden
facility: Skanes universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Solna
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: