Phase 1, First-in-Human Study to Assess the Safety, Tolerability and Anti-tumor Activity of CDR404 in HLA-A*02:01 Participants With MAGE-A4 Expressing Solid Tumors
Summary
CDR404 is a highly potent and specific T-cell engaging bispecific and bivalent antibody designed for the treatment of cancers positive for the tumor-associated antigen melanoma-associated antigen 4 (MAGE-A4). This is a first-in-human study designed to evaluate the safety, tolerability, and preliminary anti-tumor activity of CDR404 in adult patients who have the appropriate germline human leukocyte antigen HLA-A\*02:01 tissue marker and whose cancer is positive for MAGE-A4.
Detailed description
The CDR404-001 Phase 1 study will enrol patients with locally advanced, unresectable or metastatic tumors expressing MAGE-A4, which include advanced solid tumors, and will be conducted in multiple phases: 1. To identify the maximum tolerated dose (MTD) and pharmacologically effective dose range (PEDR) for CDR404 2. To assess preliminary evidence of anti-tumor activity of CDR404 3. To characterise the pharmacokinetics of CDR404 4. To characterise the immunogenicity of CDR404 5. To assess translational biomarkers
Arms & interventions
- BiologicalCDR404
IV infusions
Outcome measures
Primary
Presence of dose limiting toxicities (DLTs)
per Protocol
Time frame: From first dose to DLT period (21 days)
Incidence and severity of (serious) adverse events ([S]AEs)
AEs, SAEs
Time frame: From first dose to 90 days after the last dose
Anti-tumor response: Overall Response Rate (ORR)
per RECIST 1.1
Time frame: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Secondary
Disease control rate (DCR)
Time frame: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Duration of response (DOR)
Time frame: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Progression-free Survival (PFS)
Time frame: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Overall Survival (OS)
Time frame: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Maximum serum concentration of CDR404 (Cmax)
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Time to maximum serum concentration of CDR404 (Tmax)
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Trough serum concentration of CDR404 (Ctrough)
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Half-life of CDR404 (t1/2)
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Area under the CDR404 serum concentration over time curve (AUC0-T)
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Volume of CDR404 distribution (Vd)
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Average serum concentration of CDR404 (Cavg)
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Serum drug levels of CDR404 at steady state (CL)
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Accumulation ratio of CDR404 (Rac)
Time frame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Immunogenicity
Time frame: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Eligibility criteria
Study locations (4)
University of Miami
Miami, Florida, 33136
University of Michigan
Ann Arbor, Michigan, 48109
Providence Cancer Institute
Portland, Oregon, 97213
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19106