Clinical trial NCT06402201: First in Human Study of CDR404 in HLA-A*02:01 Participants With MAGE-A4 Expressing Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Select Advanced Solid Tumors
Lead sponsor: CDR-Life AG
Sponsor class: INDUSTRY
First posted: 2024-05-07
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: IV dose escalation
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Presence of dose limiting toxicities (DLTs)
timeFrame: From first dose to DLT period (21 days)
measure: Incidence and severity of (serious) adverse events ([S]AEs)
timeFrame: From first dose to 90 days after the last dose
measure: Anti-tumor response: Overall Response Rate (ORR)
timeFrame: 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 outcomes:
measure: Disease control rate (DCR)
timeFrame: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
measure: Duration of response (DOR)
timeFrame: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
measure: Progression-free Survival (PFS)
timeFrame: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
measure: Overall Survival (OS)
timeFrame: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
measure: Maximum serum concentration of CDR404 (Cmax)
timeFrame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
measure: Time to maximum serum concentration of CDR404 (Tmax)
timeFrame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
measure: Trough serum concentration of CDR404 (Ctrough)
timeFrame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
measure: Half-life of CDR404 (t1/2)
timeFrame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
measure: Area under the CDR404 serum concentration over time curve (AUC0-T)
timeFrame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
measure: Volume of CDR404 distribution (Vd)
timeFrame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
measure: Average serum concentration of CDR404 (Cavg)
timeFrame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
measure: Serum drug levels of CDR404 at steady state (CL)
timeFrame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
measure: Accumulation ratio of CDR404 (Rac)
timeFrame: At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)
measure: Immunogenicity
timeFrame: From first dose until date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Antwerp
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc, UCL Ouvain
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Milan
country: Italy
facility: Istituto Clinico Humanitas
city: Milan
country: Italy
facility: Isituto Europeo di Oncologia (IEO)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia, L'Hospitalet de Llobregat (ICO)
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: START Madrid
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Valencia
country: Spain
facility: Instituto de Investigacion Sanitaria (INCLIVA)
Study officials:
References: