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

Select Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06402201
• Other study ID #: CDR404-001
• Status: Recruiting
• Phase: Phase 1
• Start date: May 24, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: June 2024
• Source: CDR-Life AG
• Contact: Shet Biswas Chief Medical Officer, CDR-Life
• Phone: +41 44 515 98 98
• Email: CDR404-001_Study[@]CDR-Life.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: December 31, 2027
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Select Advanced Solid Tumors

Intervention

Biological:
• CDR404
IV infusions

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Miami	Miami	Florida
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Providence Cancer Institute	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
CDR-Life AG

Countries where clinical trial is conducted

United States,  Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of dose limiting toxicities (DLTs)	per Protocol	From first dose to DLT period (21 days)
Primary	Incidence and severity of (serious) adverse events ([S]AEs)	AEs, SAEs	From first dose to 90 days after the last dose
Primary	Anti-tumor response: Overall Response Rate (ORR)	per RECIST 1.1	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)	per RECIST 1.1	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	Duration of response (DOR)	per RECIST 1.1	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	Progression-free Survival (PFS)	per RECIST 1.1	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	Overall Survival (OS)	per RECIST 1.1	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	Maximum serum concentration of CDR404 (Cmax)	following single and multiple dose administration	At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Secondary	Time to maximum serum concentration of CDR404 (Tmax)	following single and multiple dose administration	At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Secondary	Trough serum concentration of CDR404 (Ctrough)	following single and multiple dose administration	At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Secondary	Half-life of CDR404 (t1/2)	following single and multiple dose administration	At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Secondary	Area under the CDR404 serum concentration over time curve (AUC0-T)	to the end of the dosing interval following single and multiple dose administration	At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Secondary	Volume of CDR404 distribution (Vd)	following single and multiple dose administration	At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Secondary	Average serum concentration of CDR404 (Cavg)	following single and multiple dose administration	At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Secondary	Serum drug levels of CDR404 at steady state (CL)	following single and multiple dose administration	At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Secondary	Accumulation ratio of CDR404 (Rac)	following single and multiple dose administration	At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
Secondary	Immunogenicity	Incidence of detectable anti-CDR404 antibodies (ADAs)	From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months