To evaluate the safety and tolerability of AMG 404, a monoclonal antibody that binds to PD-1 and inhibits its engagement with ligands, in patients with advanced solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
171
AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
Toxicities were graded with the Common Terminology Criteria for Adverse Events CTCAE v5.0., the following toxicities were classified as DLTs: * Any treatment related grade 5 toxicity * Grade 4 neutropenia or thrombocytopenia * Febrile neutropenia * Grade 4 anemia * Grade 3 or 4 non-hematologic toxicity * Recurrent grade 2 pneumonitis * Any other toxicity requiring permanent discontinuation of AMG 404.
Time frame: Up to Day 28
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
A TEAE is any adverse event (AE) starting on or after the first administration of investigational product (IP) and up to and including 140 days after the last IP dose date or end of the study, whichever occurs earlier. A TEAE with unknown/missing relatedness to AMG 404 is assumed as an event is related to AMG 404. A serious adverse event (SAE) is defined as an adverse event that: is fatal, is life threatening, requires in-patient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and other medically important serious event. A treatment-related AE (TRAE) is any TEAE that per investigator review has a reasonable possibility of being caused by the investigational product. In the unlikely event that the relationship is missing, the TEAE will be considered TRAE and documented in a footnote of the treatment-related summary.
Time frame: Up to the last dose of AMG 404 + 140 days (approximately 46 months); median (min, max) exposure to AMG 404 was 3.58 (0.02, 41.7) months
AMG 404 Pharmacokinetic (PK) Parameter by Dose Group: Maximum Observed Serum Concentration (Cmax) During Cycle 1 and 2
Maximum concentration of AMG 404 in blood serum at different time points.
Time frame: Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length)
AMG 404 PK Parameter by Dose Group: Time to Achieve Cmax (Tmax) During Cycle 1 and 2
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Sarcoma Oncology Research Center LLC
Santa Monica, California, United States
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, United States
University of Louisville James Graham Brown Cancer Center
Louisville, Kentucky, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Chris OBrien Lifehouse
Camperdown, New South Wales, Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia
Universitair Ziekenhuis Antwerpen
Edegem, Belgium
Nucleo de Oncologia da Bahia
Salvador, Estado de Bahia, Brazil
Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, Brazil
...and 24 more locations
Tmax represents the time to reach Cmax in the blood serum.
Time frame: Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length)
AMG 404 PK Parameter by Dose Group: Area Under the Serum Concentration-time Curve From Day 0 to Day 28 (AUC0-28d) During Cycle 1 and 2
Assessment of AMG 404 exposure over 28 days.
Time frame: Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length)
Number of Participants With Anti-AMG 404 Antibodies
Transient was defined as the number of participants with negative result at the participant's last time point tested within the study period. Only participants with both baseline and post-baseline are included.
Time frame: Day 1 pre-dose and Day 15
Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1
Objective response was defined as a tumor response assessment of either complete response (CR) (disappearance of all target lesions) or partial response (PR) (at least a 30% decrease in the sum of the diameters of target lesions) measured by positron emission tomography(PET)/computed tomography (CT), CT or magnetic resonance imaging (MRI) and assessed per RECIST v1.1. Participants who did not experience PR/CR or did not have any follow-up tumor assessments was regarded as non-responders. This endpoint was determined only for participants with measurable disease at baseline.
Time frame: Up to approximately 54 months
Duration of Response (DOR) Per Modified RECIST v1.1
DOR was defined as the time from the first documentation of objective response (CR or PR) until the first documentation of disease progression or death due to any cause, whichever occurred first. Only participants who achieved objective response were evaluated for DOR. DOR was censored at the last evaluable post-baseline tumor assessment date; otherwise, at the first dose of IP. Kaplan-Meier (KM) analysis was used to estimate DOR for responders, providing a median value and 80% confidence intervals (CI) where sufficient data were available. The Brookmeyer and Crowley method was used to calculate confidence intervals. For cohorts with limited responders or heavily censored data, the median DOR or CI bounds could not be calculated.
Time frame: Up to approximately 43 months
Disease Control Rate (DCR) Per Modified RECIST v1.1
DCR was defined as the percentage of participants in whom objective response (CR or PR) or stable disease (SD) was determined as per RECIST v1.1.
Time frame: Up to approximately 54 months
Duration of Stable Disease (DoSD) Per Modified RECIST v1.1
DoSD was measured from the start of treatment until the first documentation of disease progression or death due to any cause. DoSD was calculated only in participants with the best overall response of SD, defined as neither sufficient shrinkage to qualify PR nor sufficient increase to qualify for PD. KM analysis was used to estimate the median DoSD, and CIs were calculated using the Brookmeyer and Crowley method. DoSD was censored at the last evaluable post-baseline tumor assessment date or at the first dose of IP, if no progression or death was documented.
Time frame: Up to approximately 54 months
Progression-free Survival (PFS) Per Modified RECIST v1.1
PFS was defined as the time from the first dose of IP unite the first documentation of radiological disease progression or death due to any cause, whichever occurred first in the absence of subsequent anticancer therapy.
Time frame: Up to approximately 48 months