This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of AMG 340, a PSMA x CD3 T-cell engaging bispecific antibody, in subjects with metastatic castrate-resistant prostate cancer (mCRPC) who have received 2 or more prior lines of therapy. The study consists of 2 parts, a monotherapy dose escalation (Arm A) and a monotherapy dose expansion (Arm B). Once the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is identified in Arm A, Arm B will be initiated to further characterize the safety, tolerability and pharmacokinetic (PK) profile of the MTD/RP2D dose of AMG 340 monotherapy in subjects with mCRPC.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
AMG 340 is a bispecific antibody targeting prostate-specific membrane antigen (PSMA) on tumor cells and CD3 on T-cells
UCSF
San Francisco, California, United States
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, United States
Florida Cancer Specialists
Sarasota, Florida, United States
Tulane Cancer Center
New Orleans, Louisiana, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Thomas Jefferson University - Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, United States
Tennessee Oncology
Nashville, Tennessee, United States
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. A treatment-related AE (TRAE) was defined as any TEAE flagged as possibly caused by AMG 340. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. Serious TEAEs (SAEs) were any untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events.
Time frame: From enrollment up to and including a maximum of 90 days after last dose of AMG 340; median (min, max) duration was 4.3 (0.5, 27.1) months
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
A DLT was defined as a TEAE that was not unequivocally due to the participant's underlying malignancy or other extraneous cause, and appeared within 21 days from the first dose of AMG 340. AEs considered DLTs were: * Transient (≤72 hours) grade 3 or 4 electrolyte abnormalities, hyperglycemia, nausea/vomiting/diarrhea responsive to treatment. * Alopecia, vitiligo, and grade 3 fatigue lasting \<10 days. * Grade 3 fever lasting ≤24 hours (outside CRS context). * Grade 3 lab abnormalities resolving within 72 hours (or within 7 days for certain enzymes like ALT, GGT, ALP, and lipase). * Grade 3 CRS or TLS unresolved to ≤ grade 1 within 72 hours or any grade 4 CRS/TLS. * Prolonged grade 4 neutropenia (\>5 days) or febrile neutropenia. * Grade 3 thrombocytopenia with bleeding or any grade 4 thrombocytopenia. * Grade 4 anemia. * Grade 5 adverse events. * Lymphopenia is not considered a DLT.
Time frame: Up to approximately Day 21
Median Concentration of AMG 340
Blood samples for pharmacokinetics (PK) analysis were collected at specific time points. PK parameters were estimated using standard non-compartmental approaches.
Time frame: Cohorts 1-5: Days 1 (pre-dose to 6 hours post-dose), 2, 3, 8, and 10; Cohorts 6-10: Days 1 (pre-dose to 6 hours post-dose), 2, 3, 5 (pre-dose to 6 hours post-dose), 6, 7, 8 (pre-dose to 6 hours post-dose), 9, 10
Percentage of Participants Who Achieved an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
OR was defined as a partial response (PR) or complete response (CR) per RECIST 1.1, confirmed by a repeat assessment at least 4 weeks later. Participants who did not experience a confirmed PR/CR or did not have any follow-up tumor assessments were regarded as non-responders.
Time frame: Up to approximately 24 months
Overall Survival (OS)
OS was defined as the time from the date of study Day 1 until death due to any cause.
Time frame: Up to approximately 24 months
Prostate Specific Antigen (PSA) Progression Free Survival (PFS)
PSA PFS was defined as the interval from study day 1 to the earlier of a PSA progression or death from any cause; otherwise, PSA PFS was censored on the date of the last PSA measurement. If a participant had no baseline or post-baseline PSA measurement and a vital status of alive or unknown, PSA PFS was censored at study day 1.
Time frame: Up to approximately 24 months
Radiographic PFS (rPFS)
rPFS was defined as the interval from study day 1 to radiographic progression or death from any cause, whichever occurred first, in the absence of subsequent anti-cancer therapy; otherwise, rPFS was censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy. If a participant had no post-baseline radiographic tumor assessment and a vital status of alive or unknown, rPFS was censored at study day 1.
Time frame: Up to approximately 24 months
Percentage of Participants With rPFS at 6 Months
rPFS was defined as the interval from study day 1 to radiographic progression or death from any cause, whichever occurred first, in the absence of subsequent anti-cancer therapy; otherwise, rPFS was censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy. If a participant had no post-baseline radiographic tumor assessment and a vital status of alive or unknown, rPFS was censored at study day 1.
Time frame: 6 months
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Percentage of Participants With a 30% Reduction From Baseline in PSA (PSA30)
PSA 30 was defined as a ≥ 30% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.
Time frame: Up to approximately 24 months
Percentage of Participants With a 50% Reduction From Baseline in PSA (PSA50)
PSA 50 was defined as a ≥ 50% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.
Time frame: Up to approximately 24 months
Percentage of Participants With a 70% Reduction From Baseline in PSA (PSA70)
PSA 70 was defined as a ≥ 70% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.
Time frame: Up to approximately 24 months
Percentage of Participants With a 90% Reduction From Baseline in PSA (PSA90)
PSA 90 was defined as a ≥ 90% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.
Time frame: Up to approximately 24 months
Duration of Response (DOR) Per RECIST 1.1
DOR was defined as the time from the date of an initial objective response per RECIST 1.1, which was subsequently confirmed, until soft-tissue progression per RECIST 1.1 or death, whichever occurred first in the absence of subsequent anti-cancer therapy. Participants who had not ended their response at the time of analysis had DOR censored at their last evaluable tumor assessment by CT/MRI scan prior to subsequent anti-cancer therapy. This endpoint only applied to participants with an objective response (CR or PR) per RECIST 1.1. No participants achieved CR or PR, therefore, no participants could be analyzed for this outcome measure.
Time frame: Up to approximately 24 months
Number of Participants With Symptomatic Skeletal Events (SSE)
SSE was defined as time from study day 1 to the first symptomatic skeletal event, otherwise time to symptomatic skeletal event was censored at the last dose of AMG 340 or end of safety follow-up date, whichever was later.
Time frame: Up to approximately 24 months