This is a first-in-human Phase 1 study of DEM301 in adults with previously treated advanced metastatic colorectal cancer. DEM301 is an investigational antibody-drug conjugate. The study will evaluate the safety and tolerability of DEM301, identify doses for further study, and assess how the drug behaves in the body and whether it shows signs of activity against the cancer.
This is a Phase 1, multicenter, open-label study of DEM301 in participants with previously treated advanced metastatic colorectal cancer. The study has two parts: Dose Escalation, and Dose Expansion. Dose Escalation will evaluate the safety and tolerability of DEM301 and identify one or more recommended doses for further study. Dose Expansion will further evaluate DEM301 at the selected dose or doses. The study will also assess preliminary antitumor activity, pharmacokinetics, immunogenicity, pharmacodynamic effects, and exploratory biomarkers. Approximately 60 participants are planned.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
DEM301 is an investigational antibody-drug conjugate being evaluated as monotherapy in Dose Escalation and Dose Expansion cohorts.
Incidence of Dose-Limiting Toxicities (DLTs)
Incidence of DLTs in DLT-evaluable participants enrolled in Dose Escalation.
Time frame: 21 Days
Incidence of Adverse Events (AEs)
Incidence of AEs, including events requiring dose interruption or discontinuation, in participants enrolled in Dose Escalation and Dose Expansion.
Time frame: From first dose through 30 days after the last dose, up to approximately 24 months
Incidence of Serious Adverse Events (SAEs)
Incidence of SAEs in participants enrolled in Dose Escalation and Dose Expansion. Related SAEs occurring after the End of Treatment visit will also be reported according to the protocol.
Time frame: From signing informed consent through 30 days after the last dose, up to approximately 24 months
Maximum Tolerated Dose (MTD) of DEM301, if Applicable
The MTD of DEM301, if applicable, will be determined based on available Dose Escalation data.
Time frame: At completion of Dose Escalation, approximately 12 months
Recommended Dose(s) for Expansion (RDEs) of DEM301
One or more recommended doses for expansion will be selected based on available Dose Escalation data.
Time frame: At completion of Dose Escalation, approximately 12 months
Objective Response Rate (ORR) at 12 Weeks
ORR at 12 weeks will be assessed according to RECIST v1.1 in response-evaluable participants in Dose Escalation and Dose Expansion.
Time frame: 12 weeks
Duration of Response (DoR)
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Duration of response will be evaluated according to RECIST v1.1 in participants with a documented response in Dose Escalation and Dose Expansion.
Time frame: Up to approximately 24 months
Disease Control Rate (DCR) at 12 Weeks
DCR at 12 weeks will be assessed according to RECIST v1.1 in response-evaluable participants in Dose Escalation and Dose Expansion.
Time frame: 12 Weeks
Progression-Free Survival (PFS) at 12 Weeks
PFS at 12 weeks will be evaluated in response-evaluable participants in Dose Escalation and Dose Expansion.
Time frame: 12 Weeks
Overall Survival (OS) at 24 Weeks
OS at 24 weeks will be evaluated in participants in Dose Escalation and Dose Expansion.
Time frame: 24 Weeks
Area Under the Concentration-Time Curve (AUC) of DEM301 and Protocol-Specified Analytes
AUC will be characterized for DEM301 and protocol-specified analytes in participants in Dose Escalation and Dose Expansion.
Time frame: At protocol-specified pharmacokinetics (PK) sampling time points, up to approximately 24 months
Terminal Elimination Half-Life (t½) of DEM301 and Protocol-Specified Analytes
Terminal elimination half-life will be characterized for DEM301 and protocol-specified analytes in participants in Dose Escalation and Dose Expansion.
Time frame: At protocol-specified PK sampling time points, up to approximately 24 months
Maximum Concentration (Cmax) of DEM301 and Protocol-Specified Analytes
Maximum concentration will be characterized for DEM301 and protocol-specified analytes in participants in Dose Escalation and Dose Expansion.
Time frame: At protocol-specified PK sampling time points, up to approximately 24 months
Immunogenicity of DEM301
The presence of anti-drug antibodies and neutralizing antibodies will be evaluated in participants in Dose Escalation and Dose Expansion.
Time frame: At protocol-specified PK sampling time points, up to approximately 24 months