Natera Highlights Positive Interim Futility Analysis from Allogene Therapeutics’ MRD-Guided ALPHA3 Trial in Large B-Cell Lymphoma

AUSTIN, Texas--(BUSINESS WIRE)--Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, today highlighted Allogene Therapeutics’ (NASDAQ: ALLO) interim futility analysis from its registrational ALPHA3 trial for cemacabtagene ansegedleucel (cema-cel), an investigational allogeneic anti-CD19 CAR T therapy, in first-line (1L) consolidation large B-cell lymphoma (LBCL).

The ALPHA3 trial is enrolling patients with LBCL who test positive for molecular residual disease (MRD) following 1L therapy. These patients are then randomized either to cema-cel, an investigational allogeneic anti-CD19 CAR T therapy developed by Allogene, or observation. The interim analysis showed that 58.3% of MRD-positive patients treated with cema-cel achieved MRD clearance. In addition, at the Day-45 MRD assessment, plasma ctDNA levels decreased from baseline by a median of 97.7% in the cema-cel arm compared to a 26.6% median increase in the observation arm, suggesting molecular disease progression due to lack of intervention. These findings provide early evidence that cema-cel may help prevent or delay clinical relapse for LBCL patients with MRD.

While standard 1L chemoimmunotherapy (e.g., R-CHOP) is effective for most patients in achieving remission, approximately 30% will experience relapse. MRD assessment can identify such relapse before it shows up on imaging.¹

ALPHA3 is the first MRD-guided randomized controlled trial in LBCL. The study is designed to assess whether treatment with an allogenic CAR T product can eliminate residual disease and potentially prevent recurrence. The study identifies high-risk patients using Natera’s CLARITY^TM MRD assay, which leverages Natera’s patented phased variant MRD technology.

The interim analysis evaluated MRD clearance following treatment at a protocol-defined data cutoff. This represents another critical application for Natera’s MRD technology, providing a meaningful interim endpoint for assessing drug efficacy.

“MRD status following frontline therapy has emerged as one of the strongest predictors of relapse in LBCL, and the ALPHA3 study and cema-cel could be transformative for patients with lymphoma,” said David Kurtz, M.D., Ph.D., senior vice president & chief scientific officer, Hematology Franchise at Natera. “Pairing our ultra-sensitive phased variant MRD technology with cema-cel, pending the outcome of ALPHA 3 study, creates an actionable solution for patients who test positive for MRD at the end of 1L treatment.”

Allogene will host a conference call and webcast today at 5:30 a.m. PT / 8:30 a.m. ET to discuss the interim futility analysis. The webcast will be made available at www.allogene.com under the Investors tab in the News and Events section.

References

1. Roschewski M, Kurtz D M, Westin J R, et al: Remission Assessment by Circulating Tumor DNA in Large B-Cell Lymphoma. J Clin Oncol 10.1200/JCO-25-01534.

About Natera

Natera™ is a global leader in cell-free DNA and precision medicine, dedicated to oncology, women’s health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard-of-care to protect health and inform earlier, more targeted interventions that help lead to longer, healthier lives. Natera’s tests are supported by more than 400 peer-reviewed publications that demonstrate excellent performance. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California, and through Foresight Diagnostics, its subsidiary, operates an ISO 27001-certified and CAP-accredited laboratory certified under CLIA in Boulder, Colorado. For more information, visit www.natera.com.

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