A Study of AMG 757 in Participants With Neuroendocrine Prostate Cancer

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

Official Title
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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

Conditions
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Neuroendocrine Prostate Cancer

Intervention / Treatment
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* Drug: Tarlatamab


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Exploration<br>The maximum tolerated dose (MTD) will be estimated using isotonic regression (Ji et al, 2010). The recommended phase 2 dose (RP2D) may be identified based on emerging safety data prior to reaching an MTD. | Drug: Tarlatamab<br>* Tarlatamab will be administered as an intravenous (IV) infusion.<br>* Other names: AMG 757;|
| Experimental: Part 2: Dose Expansion<br>Participants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study. | Drug: Tarlatamab<br>* Tarlatamab will be administered as an intravenous (IV) infusion.<br>* Other names: AMG 757;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Experience One or More Treatment-emergent Adverse Events (TEAEs) |  | Day 1 to 12 months | 
| Number of Participants who Experience One or More Treatment-related Adverse Events |  | Day 1 to 12 months | 
| Number of Participants who Experience a Clinically Significant Change from Baseline in Vital Signs |  | Baseline to 12 months | 
| Number of Participants who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Measurements |  | Baseline to 12 months | 
| Number of Participants who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests |  | Baseline to 12 months | 
| Number of Participants who Experience Dose Limiting Toxicities (DLTs) |  | Baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (OR) | OR will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications. | Baseline to 12 months | 
| Duration of Response (DOR) |  | Baseline to 12 months | 
| Progression-free Survival (PFS) |  | Baseline to 12 months | 
| Overall Survival (OS) |  | Baseline to 12 months | 
| Disease Control Rate (DCR) |  | Baseline to 12 months | 
| Maximum Serum Concentration (Cmax) of Tarlatamab |  | Baseline to 12 months | 
| Minimum Serum Concentration (Cmin) of Tarlatamab |  | Baseline to 12 months | 
| Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of Tarlatamab |  | Baseline to 12 months | 
| Accumulation Ratio of Tarlatamab |  | Baseline to 12 months | 
| Half-life (t1/2) of Tarlatamab |  | Baseline to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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De novo or treatment emergent neuroendocrine prostate cancer, Non-canonical Notch ligand