CDR404 for Cancer

Recruiting at 17 trial locations

Overseen By Shet Biswas Chief Medical Officer, CDR-Life

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: CDR-Life AG

Must not be taking: Systemic steroids, Immunosuppressives

Disqualifiers: CNS metastasis, Cardiac disease, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 42

Duration: Up to 100 months

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CDR404 for certain cancers, specifically those with a protein called MAGE-A4. The goal is to determine if the treatment is safe and effective in shrinking tumors. Suitable participants have advanced solid tumors positive for MAGE-A4 and a specific tissue marker, HLA-A*02:01. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that you cannot have inadequate washout from prior anticancer therapy and cannot be on ongoing treatment with systemic steroids or other immunosuppressive therapies. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that CDR404 is likely to be safe for humans?

Research shows that CDR404 is undergoing its first human trials. No previous human studies exist to determine its tolerability or potential side effects. As an early-phase study, researchers are still assessing its safety.

Before human testing, CDR404 was studied in the lab and on animals, where it effectively targeted certain cancer cells. However, these results do not always predict its performance in humans. Since this is the first human use of CDR404, understanding its safety is a primary goal of the study. Prospective participants should consider this and discuss it with the trial team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CDR404 for cancer because it introduces a new approach to treatment through dose escalation. Unlike traditional chemotherapy and targeted therapies that often affect both healthy and cancerous cells, CDR404 aims to precisely target cancer cells, potentially reducing side effects. This innovative mechanism of action could lead to more effective and safer cancer treatments, offering hope for better patient outcomes.

What evidence suggests that CDR404 might be an effective treatment for cancer?

Research has shown that CDR404 may help fight certain types of cancer. In lab studies, CDR404 successfully killed cancer cells containing the protein MAGE-A4, found in several tumor types. This treatment boosts the immune system's T-cells, enabling them to better locate and destroy cancer cells. Early lab results suggest that CDR404 is more potent than some similar treatments, even at low doses. While these findings are promising, this study marks the first time CDR404 is being tested in humans, so further research is needed to confirm these effects in real patients. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors that show the MAGE-A4 marker and have the HLA-A*02:01 tissue type. Participants must be in good physical condition, have relapsed or not responded to standard treatments, and have measurable disease. They should also have proper organ function and agree to use effective contraception if applicable.

Inclusion Criteria

Provision of written informed consent

My organs are working well.

I am fully active or have some restrictions but can still care for myself.

Exclusion Criteria

I am currently taking steroids or other drugs that weaken my immune system.

I have brain metastases that are causing symptoms or have not been treated.

I have had surgery recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of CDR404 to identify the maximum tolerated dose and pharmacologically effective dose range

6 weeks

Multiple visits (in-person) during each 21-day cycle

Treatment

Participants continue receiving CDR404 to assess anti-tumor activity, pharmacokinetics, and immunogenicity

Up to 100 months

Regular visits (in-person) every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after the last dose

What Are the Treatments Tested in This Trial?

Interventions

• CDR404

Trial Overview CDR404, a new antibody designed to target cancers expressing the MAGE-A4 antigen, is being tested for safety and effectiveness. This first-in-human study will assess how well CDR404 works against these specific tumors in participants with the right genetic markers.

How Is the Trial Designed?

Group I: CDR404 Experimental Treatment 1 Intervention

Dose escalation

Who Is Running the Clinical Trial?

CDR-Life AG

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

The oncolytic adenoviral construct AdEHCD40L significantly inhibited the growth of CD40+ human breast cancer cells by up to 80% in vitro, demonstrating its potential as an effective treatment option.

In vivo studies showed that intratumoral injections of AdEHCD40L reduced tumor growth by over 99% in mouse models, outperforming both the parental virus and recombinant CD40L protein, indicating strong antitumor activity and enhanced apoptosis in cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of an oncolytic adenoviral-CD40 ligand (CD154) transgene construct in human breast cancer cells. Gomes, EM., Rodrigues, MS., Phadke, AP., et al.[2022]

CD40 is a crucial molecule that can influence both immune responses and cancer cell behavior, acting differently depending on the type of cell and its environment.

Preliminary clinical trials suggest that targeting CD40 with antibodies can enhance immune modulation and potentially lead to positive clinical outcomes in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology and clinical applications of CD40 in cancer treatment. Fonsatti, E., Maio, M., Altomonte, M., et al.[2017]

ABBV-428, a tumor-targeted bispecific antibody, demonstrated an acceptable safety profile in a phase I study with 59 patients, showing no maximum tolerated dose reached and only mild infusion-related reactions reported.

Despite its safety, ABBV-428 showed minimal clinical activity in treating advanced mesothelioma and ovarian cancer, with only 36% of patients achieving stable disease, indicating that while the drug is safe, its effectiveness may need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of ABBV-428, a mesothelin-CD40 bispecific, in patients with advanced solid tumors. Luke, JJ., Barlesi, F., Chung, K., et al.[2023]

In a study of 54 patients with locally advanced breast cancer (LABC) who underwent neoadjuvant chemotherapy, high levels of CXCR4 overexpression in cancer specimens were linked to significantly worse outcomes, including higher rates of recurrence and cancer death.

Patients with high CXCR4 levels had a 27.3-fold increased risk of recurrence and a 4.8-fold increased risk of death compared to those with low CXCR4 levels, indicating that CXCR4 could serve as a valuable molecular predictor for identifying at-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevated chemokine receptor CXCR4 expression in primary tumors following neoadjuvant chemotherapy predicts poor outcomes for patients with locally advanced breast cancer (LABC). Holm, NT., Abreo, F., Johnson, LW., et al.[2014]

The study successfully developed anti-CCR4 antibodies that can block signaling and induce the killing of CCR4-positive tumor cells, showing promise for cancer immunotherapy.

In a mouse model of human T-cell lymphoma, treatment with these anti-CCR4 antibodies resulted in a significant survival benefit, indicating their potential effectiveness in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fully human antagonistic antibodies against CCR4 potently inhibit cell signaling and chemotaxis. Hagemann, UB., Gunnarsson, L., Géraudie, S., et al.[2021]

In a study of 37 patients with refractory/relapsed acute lymphoblastic leukemia (R/R ALL), higher levels of CXCR4 expression were found in R/R patients compared to those newly diagnosed, indicating a potential role in chemotherapy resistance.

Blocking the CXCR4/CXCL12 signaling pathway with the antagonist AMD3100 significantly enhanced the effectiveness of the chemotherapy drug vincristine, leading to increased apoptosis in leukemic cells and suggesting a promising strategy to overcome drug resistance in R/R ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The CXCR4 Antagonist, AMD3100, Reverses Mesenchymal Stem Cell-Mediated Drug Resistance in Relapsed/Refractory Acute Lymphoblastic Leukemia. Wang, S., Wang, X., Liu, S., et al.[2022]

The expression of specific proteins, hENT1 and dCK, in pancreatic ductal adenocarcinoma (PDAC) tumors can predict the effectiveness of adjuvant gemcitabine therapy, helping to tailor treatment for patients after surgery.

The chemokine receptor CXCR4 is identified as a negative prognostic factor for survival and is linked to patterns of tumor recurrence, suggesting that therapies targeting CXCR4 could enhance treatment outcomes when combined with traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards a tailored therapy in pancreatic cancer. Maréchal, R., Van Laethem, JL.[2022]

The study found that CXCR4 surface expression on breast cancer cells does not correlate with the cells' invasiveness, suggesting that other factors may influence tumor aggressiveness.

MDA-MB-175VII cells, which have lower invasiveness, showed greater binding to anti-CXCR4 labeled liposomes and experienced more cell death compared to HCC1500 cells, indicating that targeting CXCR4 could enhance the efficacy of liposomal therapeutics in treating breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using breast cancer cell CXCR4 surface expression to predict liposome binding and cytotoxicity. Guo, P., You, JO., Yang, J., et al.[2021]

CD40 is a promising new target for cancer treatment, as it plays a role in activating immune responses through its interaction with CD40L, and various therapeutic approaches are being tested, including agonistic monoclonal antibodies.

Early clinical trials of agonistic CD40 antibodies show they are generally safe with manageable side effects, such as cytokine release syndrome and hepatotoxicity, while also demonstrating encouraging anti-tumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New emerging targets in cancer immunotherapy: the role of Cluster of Differentiation 40 (CD40/TNFR5). Piechutta, M., Berghoff, AS.[2021]

CD40 activation has been shown to promote the death of tumor cells and stimulate immune responses, making it a promising target for cancer therapies, particularly in B-cell malignancies and solid tumors.

Preclinical studies and early clinical trials suggest that therapies targeting CD40, such as agonistic antibodies and recombinant CD40L, can inhibit tumor growth and enhance immune responses, although the exact role of CD40 in cancer progression remains complex and not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD40 activation as potential tool in malignant neoplasms. Ottaiano, A., Pisano, C., De Chiara, A., et al.[2022]

CD40 is a promising target for cancer therapy because it can activate the immune system and directly kill tumor cells, providing a dual mechanism of action.

Initial phase 1 clinical trials of CD40-targeting drugs in advanced cancer patients have shown encouraging results, including objective clinical responses and immune system changes, without significant toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospect of targeting the CD40 pathway for cancer therapy. Vonderheide, RH.[2021]

CD40 agonists have shown potential in cancer immunotherapy, demonstrating moderate antitumor effects in some tumors, based on early clinical trials.

The adverse events associated with CD40 agonists, such as cytokine release and hepatotoxicity, have been mostly transient and manageable, suggesting a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and clinical trial results of agonistic anti-CD40 antibodies in the treatment of malignancies. Li, DK., Wang, W.[2020]

Citations

1. cdr-life.com cdr-life.com/news_item/cdr-life-presents-promising-preclinical-data-for-novel-t-cell-engager-programs-at-aacr-annual-meeting-2025/

CDR-Life Presents Promising Preclinical Data for Novel T ... Superior Potency and Durability: CDR404 showed more potent killing of MAGE-A4-positive cancer cell lines across multiple indications, even at ...

2. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/3494/760764/Abstract-3494-Durable-and-potent-in-vitro-T-cell

Abstract 3494: Durable and potent in vitro T cell activity with ... CDR404 also showed more efficient cancer cell killing than the TCR-TCE-Fc at low E:T ratios (down to 1:1), indicating that it has the potential ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06402201

NCT06402201 | First in Human Study of CDR404 in HLA-A ... This is a first-in-human study designed to evaluate the safety, tolerability, and preliminary anti-tumor activity of CDR404 in adult patients.

4. biospace.com biospace.com/press-releases/cdr-life-presents-early-clinical-data-demonstrating-pharmacodynamic-activity-of-cdr404-a-novel-antibody-derived-t-cell-engager-targeting-mage-a4-solid-tumors

CDR-Life Presents Early Clinical Data Demonstrating ... CDR404 is an antibody-based TCE designed to target intracellular tumor antigens presented on HLA molecules. It engages MAGE-A4 peptides ...

5. withpower.com withpower.com/trial/phase-1-neoplasms-4-2024-334ad

CDR404 for Cancer · Recruiting Participants for Phase ... Despite its safety, ABBV-428 showed minimal clinical activity in treating advanced mesothelioma and ovarian cancer, with only 36% of patients achieving stable ...

6. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A723

628 First-in-human study of CDR404, a novel bivalent and ... The trial is a phase I study evaluating the safety, tolerability, pharmacokinetics (PK) and anti-tumor activity of CDR404 in HLA-A*02:01+ patients with MAGE-A4 ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03760-2/pdf

patient selection for CDR404 PFS and OS data will be presented at the meeting Safety data were consistent with the known safety profile of afatinib. Conclusions: Although three pts ...

8. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/482837

First in Human Study of CDR404 in HLA-A*02:01 ... This is a first-in-human study designed to evaluate the safety, tolerability, and preliminary anti-tumor activity of CDR404 in adult patients.