Clinical trial NCT04702737: A Study of AMG 757 in Participants With Neuroendocrine Prostate Cancer
Official title: A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of Delta-like Protein 3 Half-life Extended Bispecific T-cell Engager AMG 757 in Subjects With De Novo or Treatment Emergent Neuroendocrine Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neuroendocrine Prostate Cancer
Keywords: De novo or treatment emergent neuroendocrine prostate cancer
Non-canonical Notch ligand
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2021-01-11
Enrollment: 41
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and tolerability of Tarlatamab and will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).


Eligibility criteria: Inclusion Criteria (Part 1: Dose Exploration and Part 2: Dose Expansion):

* Participant has provided informed consent prior to initiation of any study specific activities/procedures.
* Men aged ≥ 18 years at time of signing the informed consent.
* Metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC) defined by histology, immunohistochemistry, or genomic analyses of baseline tumor tissue (by local assessment) or circulating tumor DNA (ctDNA) (by local assessment) as per protocol
* At least 1 line of prior systemic treatment per protocol.
* Participants with treatment-emergent NEPC or de novo NEPC with histologic evidence of prostate cancer with neuroendocrine differentiation without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analogue therapy during the course of protocol therapy
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Prostate Cancer Working Group 3 (PCWG3) modifications
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
* Participants with treated brain metastases are eligible provided they meet defined criteria
* Adequate organ function as defined in protocol

Exclusion Criteria (Part 1: Dose Exploration and Part 2: Dose Expansion):

* History of other malignancy within the past 2 years, with exceptions:

  * Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before enrollment and felt to be at low risk for recurrence by the treating physician
  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  * Adequately treated non-muscle invasive urothelial carcinoma
* History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥ 2 years
* Untreated or symptomatic brain metastases and leptomeningeal disease
* Anti-tumor therapy within 28 days of study day 1; concurrent use of hormone deprivation therapy for hormone refractory prostate cancer is permitted; participants on a stable bisphosphonate or denosumab prior to study day 1 are eligible

Exceptions:

* Participants who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicities have resolved to Grade ≤ 1
* Prior palliative radiotherapy must have been completed at least 7 days before the first dose of tarlatamab
* Participants who received androgen signaling inhibitor are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to Grade ≤ 1

  * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior study day 1
  * Active autoimmune disease requiring systemic treatment within the past 2 years
  * Known positive test for human immunodeficiency virus (HIV) or hepatitis
  * Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 0 or 1 (with the exception of alopecia or toxicities that are stable and well-controlled)
  * History of hypophysitis or pituitary dysfunction
  * Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  * Participants on prior delta-like ligand 3 (DLL3)-targeted therapy may be eligible if discussed with Amgen Medical Monitor prior to enrollment
  * Evidence of severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection unless agreed upon with Medical Monitor and with no acute symptoms of coronavirus disease 2019 (COVID19) disease within 14 days prior to first dose of investigational product (counted from day of positive test for asymptomatic participants).

Primary outcomes:
measure: Number of Participants who Experience One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 to 12 months
measure: Number of Participants who Experience One or More Treatment-related Adverse Events
timeFrame: Day 1 to 12 months
measure: Number of Participants who Experience a Clinically Significant Change from Baseline in Vital Signs
timeFrame: Baseline to 12 months
measure: Number of Participants who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Measurements
timeFrame: Baseline to 12 months
measure: Number of Participants who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests
timeFrame: Baseline to 12 months
measure: Number of Participants who Experience Dose Limiting Toxicities (DLTs)
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Objective Response (OR)
timeFrame: Baseline to 12 months
measure: Duration of Response (DOR)
timeFrame: Baseline to 12 months
measure: Progression-free Survival (PFS)
timeFrame: Baseline to 12 months
measure: Overall Survival (OS)
timeFrame: Baseline to 12 months
measure: Disease Control Rate (DCR)
timeFrame: Baseline to 12 months
measure: Maximum Serum Concentration (Cmax) of Tarlatamab
timeFrame: Baseline to 12 months
measure: Minimum Serum Concentration (Cmin) of Tarlatamab
timeFrame: Baseline to 12 months
measure: Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of Tarlatamab
timeFrame: Baseline to 12 months
measure: Accumulation Ratio of Tarlatamab
timeFrame: Baseline to 12 months
measure: Half-life (t1/2) of Tarlatamab
timeFrame: Baseline to 12 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: San Francisco
country: United States
facility: University of California at San Francisco Helen Diller Family Comprehensive Cancer Center
state: California
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Community Health Network MD Anderson Cancer Center - North
state: Indiana
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Camperdown
country: Australia
facility: Chris OBrien Lifehouse
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Graz
country: Austria
facility: Medizinische Universitaet Graz
city: Linz
country: Austria
facility: Ordensklinikum Linz Elisabethinen
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Villejuif Cedex
country: France
facility: Gustave Roussy
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: