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

Overview

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

• Biological CDR404
  IV infusions

Primary outcome measures

• Presence of dose limiting toxicities (DLTs) [Time frame: From first dose to DLT period (21 days)]
• Incidence and severity of (serious) adverse events ([S]AEs) [Time frame: From first dose to 90 days after the last dose]
• Anti-tumor response: Overall Response Rate (ORR) [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 outcome measures (12)

• 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)]

Eligibility criteria

Inclusion criteria

• Provision of written informed consent
• HLA-A\*02:01 positive
• MAGE-A4 positive tumor
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) \[ECOG PS\] 0 or 1
• Selected advanced solid tumors
• Relapsed from, refractory to, or intolerant of standard therapy
• Measurable disease per RECIST v1.1
• Adequate organ function
• If applicable, must agree to use highly effective contraception

Exclusion criteria

• Symptomatic or untreated central nervous system metastasis
• Inadequate washout from prior anticancer therapy
• Significant ongoing toxicity from prior anticancer treatment
• Recent surgery
• Clinically significant cardiac disease
• Active infection requiring systemic antibiotic treatment
• Human immunodeficiency virus (HIV) at risk of acquired immunodeficiency syndrome (AIDS)-related outcomes
• Active hepatitis B virus (HBV) or hepatitis C virus (HBC)
• Ongoing treatment with systemic steroids or other immunosuppressive therapies
• Significant secondary malignancy
• History of chronic or recurrent active autoimmune disease requiring treatment
• Uncontrolled intercurrent illness
• Pregnancy or lactation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 6 centers

• Hospital Universitari Vall d'Hebron — Barcelona
• Institut Catala d'Oncologia, L'Hospitalet de Llobregat (ICO) — Barcelona
• Hospital 12 de Octubre — Madrid
• START Madrid — Madrid
• Hospital Universitari i Politecnic La Fe — Valencia
• Instituto de Investigacion Sanitaria (INCLIVA) — Valencia

United States · 4 centers

• University of Miami — Miami
• University of Michigan — Ann Arbor
• Providence Cancer Institute — Portland
• Pennsylvania Hospital — Philadelphia

Belgium · 4 centers

• Universitair Ziekenhuis Antwerpen — Antwerp
• Institut Jules Bordet — Brussels
• Cliniques Universitaires Saint-Luc, UCL Ouvain — Brussels
• Universitair Ziekenhuis Gent — Ghent

Italy · 2 centers

• Istituto Clinico Humanitas — Milan
• Isituto Europeo di Oncologia (IEO) — Milan

Denmark · 1 center

• Rigshospitalet — Copenhagen

United Kingdom · 1 center

• Royal Marsden Hospital — Sutton

Identifiers

NCT: NCT06402201 · CDR404-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗