To evaluate the safety and tolerability of Tarlatamab and will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Tarlatamab will be administered as an intravenous (IV) infusion.
Mayo Clinic Arizona
Phoenix, Arizona, United States
Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs)
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.
Time frame: Up to approximately 3 years
Number of Participants Who Experienced One or More Treatment-related Adverse Events (TRAE)
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.
Time frame: Up to approximately 3 years
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
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).
Time frame: Up to 28 days
Objective Response Rate (ORR)
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.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of California at San Francisco Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
University of Chicago
Chicago, Illinois, United States
Community Health Network MD Anderson Cancer Center - North
Indianapolis, Indiana, United States
Washington University
St Louis, Missouri, United States
Weill Cornell Medical College
New York, New York, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
The Ohio State University
Columbus, Ohio, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
...and 11 more locations
Time frame: Up to approximately 3 years
Duration of Response (DOR)
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.
Time frame: Up to approximately 3 years
Radiographic Progression-free Survival (PFS)
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.
Time frame: Up to approximately 3 years
Overall Survival (OS)
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.
Time frame: Up to approximately 3 years
Disease Control Rate (DCR)
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.
Time frame: Up to approximately 3 years
Maximum Serum Concentration (Cmax) of Tarlatamab
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.
Time frame: Cycle 2 Day 1 and Day 15: Predose, end of infusion (EOI), 2, 6, 24, 48, 96 and 168 hours after EOI
Tarlatamab Concentration at the End of a Dosing Interval or Before Planned Next Dose (Ctrough)
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.
Time frame: Cycle 2 Day 15: Predose
Area Under the Concentration-time Curve Over the Dosing Interval From Time 0 to 336 Hours (AUC336) of Tarlatamab
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.
Time frame: Cycle 2 Day 1 and Day 15: Predose, EOI, 2, 6, 24, 48, 96, 168, and 336 hours after EOI
Terminal Phase Elimination Half-life (t1/2,z) of Tarlatamab
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.
Time frame: Cycle 2 Day 15: Predose, EOI, 2, 6, 24, 48, 96 and 168 hours after EOI