First in Human Study of CDR404 in HLA-A*02:01 Participants With MAGE-A4 Expressing Solid Tumors

Phase 1

Recruiting

• Conditions: Select Advanced Solid Tumors
• Interventions: Biological: CDR404

• Registration Number: NCT06402201
• Lead Sponsor: CDR-Life AG

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

Study Timeline

• Study First Submitted: 2024-04-25
• Study First Submitted QC: 2024-05-02
• Study First Posted: 2024-05-07
• Study Start: 2024-05-24
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-11
• Last Update Posted: 2025-04-15
• Primary Completion: 2026-06-30
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 42

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
CDR404	CDR404	Dose escalation

Primary Outcome Measures

Name	Time	Method
Presence of dose limiting toxicities (DLTs)	From first dose to DLT period (21 days)	per Protocol
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
Incidence and severity of (serious) adverse events ([S]AEs)	From first dose to 90 days after the last dose	AEs, SAEs

Secondary Outcome Measures

Name	Time	Method
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
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
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
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
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)
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
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
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
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
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
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
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
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

Trial Locations

Locations (17)

University of Miami; 🇺🇸 Miami, Florida, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Pennsylvania Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Universitair Ziekenhuis Antwerpen; 🇧🇪 Antwerp, Belgium

Providence Cancer Institute; 🇺🇸 Portland, Oregon, United States

Institut Jules Bordet; 🇧🇪 Brussels, Belgium

Cliniques Universitaires Saint-Luc, UCL Ouvain; 🇧🇪 Brussels, Belgium

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

Istituto Clinico Humanitas; 🇮🇹 Milan, Italy

Institut Catala d'Oncologia, L'Hospitalet de Llobregat (ICO); 🇪🇸 Barcelona, Spain

Isituto Europeo di Oncologia (IEO); 🇮🇹 Milan, Italy

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

START Madrid; 🇪🇸 Madrid, Spain

Hospital Universitari i Politecnic La Fe; 🇪🇸 Valencia, Spain

Instituto de Investigacion Sanitaria (INCLIVA); 🇪🇸 Valencia, Spain