MAGE-A4 T-Cell Engager Cleared for Phase 1 Trial in Solid Tumors

Swethajit Biswas, MD, PhD

The FDA has cleared CDR-Life's investigational new drug application (IND) for its MAGE-A4 T-cell engager (TCE) therapy CDR404 to be evaluated in a phase 1 clinical trial in patients with solid tumors.¹

“CDR404 holds the potential to become the off-the-shelf therapy for multiple cancers expressing MAGE-A4 with high unmet need, including non-small cell lung cancer (NSCLC),” Christian Leisner, PhD, Chief Executive Officer, CDR-Life, said in a statement.¹ “We are thrilled to achieve this milestone and are continuing to advance several additional programs leveraging our M-gager® technology against promising intracellular cancer targets with the goal of improving patient lives.”

CDR404 is an antibody-based, bivalent and bispecific MAGE-A4 TCE developed with the use of the company’s M-gager® technology for targeting intracellular tumor antigens through the major histocompatibility complex. CDR-Life expects to initiate enrollment in the phase 1 trial in the coming months. CDR404 is the company’s lead candidate developed with the M-gager technology, which it is also using to develop 3 other therapies for undisclosed solid tumors targets: CDR505, CDR106, and CDR304.CDR-Life also has CDR101, a trispecific next-generation local activator and TCE therapy targeted BCMA, CD3, and PD-L1 for the treatment of relapsed/refractory multiple myeloma (RRMM), in lead preclinical studies.

CDR-Life recently presented promising preclinical data on CDR404 in MAGE-A4+ squamous (SQ) NSCLC at the Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting, held November 1-5, 2023, in San Diego, California. The data were presented in 2 posters and explored MAGE-A4 expression in solid cancers and Quantitative Systems Pharmacology.²

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“The absence of actionable genetic alterations makes SQ-NSCLC a difficult-to-treat cancer after relapse from immune checkpoint blockade. The demonstration of high MAGE-A4 protein expression in SQ-NSCLC and potent preclinical cytotoxicity of CDR404, highlights the therapeutic promise of CDR404 in HLA-A*02:01+ patients with SQ-NSCLC. Results from the second presentation show that leveraging the QSP model for the prediction of CDR404 doses that are likely to be safe and efficacious will enable CDR-Life to select the most effective dose to carry forward into a future registrational study,” Swethajit Biswas, MD, PhD, Chief Medical Officer, CDR-Life, said in an earlier statement.²

The research found that SQ-NSCLC had the highest MAGE-A4 mRNA expression levels among solid cancers in the The Cancer Genome Atlas database, with positive immunohistochemistry in 28/50 SQ-NSCLC samples. Four different doses of CDR404 induced complete tumor regression in the in vivo SQ-NSCLC NCI-H1703 xenograft model. In another model, the QSP model predicted doses of CDR404 which might have the most favorable benefit-risk profile for patients in the upcoming phase 1 trial.²

“These milestones underscore the continued advancement of CDR404’s potential as an off-the-shelf precision immunotherapy for MAGE-A4+ solid tumors. The unique Fab-(scFv)2 molecular format and CD3 binding properties of CDR404 isvery different compared to previous T-cell engagers which have targeted MAGE-A4+ tumors, thereby optimizing the probability-of-success in the clinic,” Biswas said.²

REFERENCES

1. CDR-Life Announces FDA Clearance of IND Application for CDR404 for Treatment of Solid Tumors. News release. CDR-Life. January 23, 2024. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.cdr-life.com/wp-content/uploads/2024/01/CDR404-IND-Approval-PR.pdf
2. CDR-Life Presents Findings from Two Studies in Preparation of Phase 1 Trial with Immunotherapy CDR404 for Treatment of Solid Tumors at SITC 2023. News release. November 3, 2023. https://www.cdr-life.com/wp-content/uploads/2023/11/CDRLife_SITC-2023-Press-Release_103023.pdf