This study has been transitioned to CTIS with ID 2024-513316-10-00 check the CTIS register for the current data. Primary:• To Evaluate the safety and tolerability of tarlatamab • Determine the maximum tolerated dose (MTD) or recommended phase 2 dose…
ID
Source
Brief title
Condition
- Other condition
- Prostatic disorders (excl infections and inflammations)
Synonym
Health condition
neuro-endocriene prostaatkanker
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Treatment-emergent adverse events, treatment-related adverse events, and
changes in vital signs, electrocardiogram (ECG), and
clinical laboratory tests
2. Dose limiting toxicities (DLTs)
Secondary outcome
1. o Objective response (OR) per Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1
o Duration of response (DOR) per RECIST 1.1
o Radiographic Progression-free survival (PFS) per Prostate Cancer Working
Group 3 (PCWG3)
o Overall survival (OS)
o Disease Control Rate (DCR) per RECIST 1.1
2. PK parameters for tarlatamab following intravenous (IV) administration
including, but not limited to, maximum serum concentration (Cmax), minimum
serum concentration (Cmin), area under the concentration-time curve (AUC) over
the dosing interval, accumulation ratio, and half-life (t1/2)
Background summary
Tarlatamab (AMG 757) is a half-life extended (HLE) bispecific T cell engager
(BiTE®) antibody designed to direct T-effector cell to DLL3 expressing cells.
Currently, a first in human phase 1 study evaluating the safety, tolerability
and pharmacokinetics of tarlatamab in subjects with SMLC (Study 20160323) is
ongoing. Tarlatamab demonstrated potent cell killing against DLL3 expressing
SCLC and other neuroendocrine tumor cell lines in vitro, including the NEPC
cell line, NCI-H660.
A detailed description of the chemistry, pharmacology, nonclinical
pharmacokinetics, and toxicology of tarlatamab is provided in the tarlatamab
Investigator*s Brochure.
Please refer to section 2.2 of the protocol.
Study objective
This study has been transitioned to CTIS with ID 2024-513316-10-00 check the CTIS register for the current data.
Primary:
• To Evaluate the safety and tolerability of tarlatamab
• Determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
Secondary:
• Evaluate anti-tumor activity of tarlatamab as assessed by additional
measures
• Characterize the pharmacokinetics (PK) tarlatamab
Study design
This is an open label phase 1b study evaluating tarlatamab monotherapy.
Tarlatamab will be administered as a short-term IV infusion Q2W (with step
dosing) in a 28-day cycle as monotherapy in subjects with de novo or
treatment-emergent NEPC.
The study will consist of 2 parts: dose exploration (Part 1) and dose
expansion (Part 2).
Intervention
Tarlatamab will be administered as a short-term IV infusion Q2W (with step
dosing) in a 28-day cycle as monotherapy
Study burden and risks
Please refer to section E2 and E9.
Minervum 7061
Breda 4817 ZK
NL
Minervum 7061
Breda 4817 ZK
NL
Listed location countries
Age
Inclusion criteria
o Adult subjects (>= 18 years of age) with metastatic de novo or
treatment-emergent NEPC
defined as one or more of the following will be eligible to enroll:
histological diagnosis of
small cell NEPC, prostate carcinoma with neuroendocrine differentiation as
defined by
positive immunohistochemical staining for chromogranin and/or synaptophysin in
the
majority of the tumor sample or >= 2 alterations in Tp53, RB1, and/or PTEN by
immunohistochemistry (IHC) or genomic analyses of baseline tumor tissue or
circulating
tumor DNA (ctDNA).
o Subjects are required to have progressed on at least 1 line of prior
treatment, including a platinum containing regimen for de novo NEPC (if at the
time of
NEPC diagnosis they had no prior diagnosis or treatment for prostate carcinoma)
or an
androgen signaling inhibitor (eg, abiraterone, enzalutamide, and/or
apalutamide) if
treatment-emergent (had a previous diagnosis of prostate carcinoma prior to NEPC
diagnosis).
o Subjects must have measurable disease per Response Evaluation Criteria
in Solid Tumors (RECIST) 1.1 criteria with Prostate Cancer Working Group 3
(PCWG3)
guidelines, have an Eastern Cooperative Oncology Group (ECOG) performance
status of
<= 2, and adequate organ function.
For a full list of eligibility criteria, please refer to Section 5.1 to Section
5.2 of the protocol.
Exclusion criteria
-History of other malignancy within the past 2 years
-Untreated (includes new lesions or progression in previously treated lesions)
or symptomatic brain metastases and leptomeningeal disease
-History or presence of relevant CNS pathology such as uncontrolled epilepsy or
seizure disorder, aphasia, paresis, dementia, severe brain injuries,
Parkinson*s disease, cerebellar disease, organic brain disorder, or psychosis
-Myocardial infarction within 12 months of study day 1, symptomatic congestive
heart failure (New York Heart Association > class II), unstable angina, or
clinically significant uncontrolled cardiac arrhythmia
-History of arterial thrombosis (eg, stroke or transient ischemic attack)
within 12 months of first dose of tarlatamab
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-513316-10-00 |
| EudraCT | EUCTR2020-003508-15-NL |
| ClinicalTrials.gov | NCT04702737 |
| CCMO | NL75623.056.20 |