Select Advanced Solid Tumors
Conditions
Brief 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
Interventions
BIOLOGICALCDR404
IV infusions
Sponsors
CDR-Life AG
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
IV dose escalation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provision of written informed consent 2. HLA-A\*02:01 positive 3. MAGE-A4 positive tumor 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) \[ECOG PS\] 0 or 1 5. Selected advanced solid tumors 6. Relapsed from, refractory to, or intolerant of standard therapy 7. Measurable disease per RECIST v1.1 8. Adequate organ function 9. If applicable, must agree to use highly effective contraception
Exclusion criteria
1. Symptomatic or untreated central nervous system metastasis 2. Inadequate washout from prior anticancer therapy 3. Significant ongoing toxicity from prior anticancer treatment 4. Recent surgery 5. Clinically significant cardiac disease 6. Active infection requiring systemic antibiotic treatment 7. Human immunodeficiency virus (HIV) at risk of acquired immunodeficiency syndrome (AIDS)-related outcomes 8. Active hepatitis B virus (HBV) or hepatitis C virus (HBC) 9. Ongoing treatment with systemic steroids or other immunosuppressive therapies 10. Significant secondary malignancy 11. History of chronic or recurrent active autoimmune disease requiring treatment 12. Uncontrolled intercurrent illness 13. Pregnancy or lactation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Presence of dose limiting toxicities (DLTs) | From first dose to DLT period (21 days) | per Protocol |
| Incidence and severity of (serious) adverse events ([S]AEs) | From first dose to 90 days after the last dose | AEs, SAEs |
| Anti-tumor response: Overall Response Rate (ORR) | From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months | per RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months | per RECIST 1.1 |
| Duration of response (DOR) | From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months | per RECIST 1.1 |
| Progression-free Survival (PFS) | From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months | per RECIST 1.1 |
| Overall Survival (OS) | From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months | per RECIST 1.1 |
| Maximum serum concentration of CDR404 (Cmax) | At the end of Cycle 1 and Cycle 2 (each cycle is 21 days) | following single and multiple dose administration |
| Time to maximum serum concentration of CDR404 (Tmax) | At the end of Cycle 1 and Cycle 2 (each cycle is 21 days) | following single and multiple dose administration |
| Trough serum concentration of CDR404 (Ctrough) | At the end of Cycle 1 and Cycle 2 (each cycle is 21 days) | following single and multiple dose administration |
| Half-life of CDR404 (t1/2) | At the end of Cycle 1 and Cycle 2 (each cycle is 21 days) | following single and multiple dose administration |
| Area under the CDR404 serum concentration over time curve (AUC0-T) | At the end of Cycle 1 and Cycle 2 (each cycle is 21 days) | to the end of the dosing interval following single and multiple dose administration |
| Volume of CDR404 distribution (Vd) | At the end of Cycle 1 and Cycle 2 (each cycle is 21 days) | following single and multiple dose administration |
| Average serum concentration of CDR404 (Cavg) | At the end of Cycle 1 and Cycle 2 (each cycle is 21 days) | following single and multiple dose administration |
| Serum drug levels of CDR404 at steady state (CL) | At the end of Cycle 1 and Cycle 2 (each cycle is 21 days) | following single and multiple dose administration |
| Accumulation ratio of CDR404 (Rac) | At the end of Cycle 1 and Cycle 2 (each cycle is 21 days) | following single and multiple dose administration |
| Immunogenicity | From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months | Incidence of detectable anti-CDR404 antibodies (ADAs) |
Countries
Belgium, Denmark, Italy, Spain, United Kingdom, United States
Contacts
CONTACTDimitrios Chondros Chief Medical Officer, CDR-Life
Outcome results
None listed