A Study of AMG 757 in Participants With Neuroendocrine Prostate Cancer

Phase 1

Completed

Conditions: Neuroendocrine Prostate Cancer

Interventions: Drug: Tarlatamab

Registration Number: NCT04702737

Lead Sponsor: Amgen

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 41

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1: Dose Exploration	Tarlatamab	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.
Part 2: Dose Expansion	Tarlatamab	Participants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs)	Up to approximately 3 years	An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an AE starting on or after the first dose of tarlatamab, and up to and including 47 days after the last dose of tarlatamab excluding the events reported after End of Study date. Clinically significant changes from baseline in vital signs, 12-lead electrocardiograms (ECGs) and clinical laboratory tests were also reported as TEAEs.
Number of Participants Who Experienced One or More Treatment-related Adverse Events (TRAE)	Up to approximately 3 years	A TRAE was defined as a TEAE that per investigator review had a reasonable possibility of being caused by tarlatamab. Clinically significant changes from baseline in vital signs, 12-lead ECGs and clinical laboratory tests were also reported as TEAEs.
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)	Up to 28 days	A DLT was defined as any qualifying toxicity that was at least possibly related to tarlatamab with an onset within the first 28 days following first dose with either of the following criteria: 1. Grade 3 adverse event lasting more than 3 days (with the exception of fatigue and Grade 3 non-febrile neutropenia that improved to ≤ Grade 1 within 3 weeks including the use of growth factor support per neutropenia management guidelines); 2. ≥ Grade 4 adverse event regardless of duration (with the exception of grade 4 non-febrile neutropenia lasting less than or equal to 7 days including the use of growth factor support per neutropenia management guidelines).

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to approximately 3 years	OR was assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications. OR was defined as best overall response of partial response (PR) or complete response (CR) per RECIST 1.1, confirmed by an assessment at least 4 weeks later. Participants who did not experience a PR/CR or did not have any follow-up tumor assessments were regarded as non-responders. ORR was defined as the percentage of participants with a best overall response of confirmed CR or PR per RECIST 1.1. The percentage of participants with an OR was summarized along with the Clopper-Pearson (Clopper and Pearson, 1934) exact 95% confidence interval (CI). The result reported was evaluated by central reviewer assessment.
Duration of Response (DOR)	Up to approximately 3 years	DOR was defined as the time from the date of an initial objective response to the earlier of progressive disease or death for participants with an objective response per RECIST 1.1. DOR was assessed per RECIST 1.1 with PCWG3 modifications. The distribution of DOR was summarized using the Kaplan-Meier (KM) method with CI calculated using the Brookmeyer and Crowley (Brookmeyer and Crowley, 1982) method. The result reported was evaluated by central reviewer assessment.
Radiographic Progression-free Survival (PFS)	Up to approximately 3 years	Radiographic PFS was defined as the interval from the first dose of tarlatamab to the earlier of a radiographic progression or death from any cause. Radiographic PFS was assessed per RECIST 1.1 with PCWG3 modifications. The distribution of radiographic PFS was summarized using the KM method with CI calculated using the Brookmeyer and Crowley (Brookmeyer and Crowley, 1982) method. The result reported was evaluated by central reviewer assessment.
Overall Survival (OS)	Up to approximately 3 years	OS was defined as the time from the start of treatment until event of death due to any cause. The distribution of OS was summarized using the KM method with CI calculated using the Brookmeyer and Crowley (Brookmeyer and Crowley, 1982) method.
Disease Control Rate (DCR)	Up to approximately 3 years	DCR was defined as the percentage of participants with a best overall response of confirmed response (CR/PR) or stable disease (SD) as per RECIST 1.1. The DCR was assessed per RECIST 1.1. The percentage of participants with disease control with corresponding exact 95% CI was calculated using the Clopper-Pearson (Clopper and Pearson, 1934) method. The result reported was evaluated by central reviewer assessment.
Maximum Serum Concentration (Cmax) of Tarlatamab	Cycle 2 Day 1 and Day 15: Predose, end of infusion (EOI), 2, 6, 24, 48, 96 and 168 hours after EOI	Pharmacokinetic (PK) parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.
Tarlatamab Concentration at the End of a Dosing Interval or Before Planned Next Dose (Ctrough)	Cycle 2 Day 15: Predose	PK parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. The result for this endpoint is given for cycle 2 only.
Area Under the Concentration-time Curve Over the Dosing Interval From Time 0 to 336 Hours (AUC336) of Tarlatamab	Cycle 2 Day 1 and Day 15: Predose, EOI, 2, 6, 24, 48, 96, 168, and 336 hours after EOI	PK parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. The result for this endpoint is given for cycle 2 only.
Terminal Phase Elimination Half-life (t1/2,z) of Tarlatamab	Cycle 2 Day 15: Predose, EOI, 2, 6, 24, 48, 96 and 168 hours after EOI	PK parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. The result for this endpoint is given for cycle 2 only.

Trial Locations

Locations (21): Mayo Clinic Arizona
🇺🇸
Phoenix, Arizona, United States
University of California at San Francisco Helen Diller Family Comprehensive Cancer Center
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San Francisco, California, United States
Winship Cancer Institute of Emory University
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Atlanta, Georgia, United States
University of Chicago
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Chicago, Illinois, United States
Community Health Network MD Anderson Cancer Center - North
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Indianapolis, Indiana, United States
Washington University
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St Louis, Missouri, United States
Weill Cornell Medical College
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New York, New York, United States
Wake Forest University Health Sciences
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Winston-Salem, North Carolina, United States
The Ohio State University
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Columbus, Ohio, United States
University of Texas MD Anderson Cancer Center
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Houston, Texas, United States
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Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States