A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of AGS-22M6E or ASG-22CE Given as Monotherapy Followed by Expansion Cohorts in Subjects With Malignant Solid Tumors That Express Nectin-4
AGS-22M6E and ASG-22CE are fully human monoclonal antibody conjugated to a cytotoxic agent
monomethyl auristatin E (MMAE) targeting Nectin-4 (Agensys code name AGS-22). The main
difference between AGS-22M6E and ASG-22CE is the change in cell line for antibody
production. AGS-22M6E and ASG-22CE will be administered at mg/kg doses based on the subjects
weight at baseline and doses will not change unless the subjects weight changes by ≥ 10%
from their baseline weight or the investigational product Dosage Assessment criteria is met.
Subjects will be prescreened for Nectin-4 expression prior to undergoing screening
procedures for the main study. Subjects with tumors positive for Nectin-4 expression may be
screened for eligibility into the main study. The dose escalation period is estimated to
take between 12 and 18 months depending on whether 3 or 6 subjects are enrolled in a given
dose cohort, and the availability of consenting subjects.
Subjects will be treated in the dose escalation phase of the study until the maximum
tolerated dose (MTD) and recommended dose for expansion (RDE) has been determined by the
data review team (DRT). After the RDE has been determined, subjects will be enrolled into 1
of 3 expansion cohorts. There will be 3 expansion cohorts, each targeting a specific cancer
(i.e.,Breast, Bladder and Lung plus other solid tumor cancers). The DRT may recommend
stopping the study, adjusting the dose or amending the trial at any time.
The clinical bridging to the ASG-22CE involves treating the subjects with ASG-22CE,
irrespective of cancer type, at the next lowest dose level previously determined to be safe
for AGS-22M6E. After the initial subjects are treated at the bridging dose with ASG-22CE
and have completed the safety assessment, future subjects will only be treated with ASG-22CE
throughout the remainder of the study.
A disease assessment will be performed by the investigator at Week 8 (± 14 days). Subjects
without evidence of disease progression may continue to receive treatment until disease
progression or intolerability.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of adverse events
Up to 28 days after the last dose of study drug
United States: Food and Drug Administration
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|Emory University||Atlanta, Georgia 30322|
|Karmanos Cancer Institute||Detroit, Michigan 48201|
|University of North Carolina, Chapel Hill||Chapel Hill, North Carolina 27599|
|University of Colorado, Denver-Aurora||Aurora, Colorado 80045|