Press Release
Allogene Therapeutics and Foresight Diagnostics Announce Partnership to Develop MRD-based In-Vitro Diagnostic for Use in ALPHA3, the First Pivotal Trial for Frontline Consolidation in Large B-Cell Lymphoma
- Partnership Will Utilize Foresight’s Ultra-Sensitive MRD Technology to Identify Patients for Enrollment in Allogene’s ALPHA3 Trial
The ALPHA3 trial uses Foresight’s investigational PhasED-Seq™ ctDNA-MRD platform to identify patients with MRD after 1L treatment for LBCL. The study will evaluate whether such patients benefit from consolidation with cemacabtagene ansegedleucel, or cema-cel (previously known as ALLO-501A). If successful, cema-cel could become part of the 1L treatment plan for newly diagnosed LBCL patients who are at a high risk for recurrence. Start-up activities for the ALPHA3 trial have been initiated.
“We knew that an ultra-sensitive ctDNA-based biomarker would be crucial to accurately identify patients with minimal residual disease whose cancer will likely recur. Foresight was the partner we were waiting for due to PhasED-Seq’s robust evidence and reputation as the most reliable and sensitive MRD assay in development for LBCL,” said
Although 1L R-CHOP is curative for many with LBCL, approximately 30% of patients who initially respond will later relapsei. The standard of care after 1L treatment has been simply to “watch and wait” for the disease to relapse. The reliance on radiographic imaging, the current clinical standard for relapse detection, does not allow effective consolidation approaches due to its limited accuracyii. PhasED-Seq is an ultra-sensitive and specific, plasma-based liquid biopsy that will enable cema-cel’s 1L consolidation approach in ALPHA3 through early and accurate MRD assessment beyond current radiographic imaging-based disease assessmentiii.
Growing evidence also suggests improved outcomes and safety for patients who are treated with CAR T when tumor burden is lowiv. Cema-cel’s Phase 1 safety profile, with low rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), already permits its use in the outpatient setting in relapsed/refractory patients and may further improve in patients with no radiological evidence of disease.
“Although CAR T therapy has shown promise in multiple cancer indications, it has been relegated to later lines of treatment. The combination of cema-cel’s speed to treatment, its favorable efficacy and safety profile from the Phase 1 trial in later lines, and the ability to pair it with an accurate biomarker has provided the pathway to introduce CAR T into the first line LBCL treatment setting. Importantly, it may allow cema-cel to consolidate response in patients at high risk of relapse and in the community setting where most first line patients are managed,” said
“We commend Allogene for pioneering ctDNA biomarkers and leading the way toward personalized medicine. The ALPHA3 study showcases their commitment to advancing patient care,” said
About
About PhasED-Seq
The Foresight MRD platform is based on the Phased variant Enrichment and Detection by Sequencing (PhasED-Seq™) technology. PhasED-Seq lowers the error profile of mutation detection in sequencing data by requiring the concordant detection of two separate non-reference events in an individual DNA molecule. By detecting more than one mutation, PhasED-Seq can more accurately distinguish tumor-derived cell free DNA (i.e., ctDNA) from healthy cell free DNA – enabling detection of ctDNA at levels below one part-per-million (<0.0001%). PhasED-Seq has been extensively tested in thousands of patient samples.
About
About Cemacabtagene Ansegedleucel (Previously Known as ALLO-501A)
Cemacabtagene ansegedleucel, or cema-cel is a next generation anti-CD19 AlloCAR T™ investigational product for the treatment of large B cell lymphoma (LBCL). This product candidate is currently being studied in an ongoing potentially pivotal Phase 2 trial in relapsed/refractory (r/r) LBCL. The ALPHA3 pivotal Phase 2 trial in first line (1L) consolidation for the treatment of LBCL is expected to begin mid-2024. In June 2022, the U.S. Food and Drug Administration granted Regenerative Medicine Advanced Therapy (RMAT) designation to cema-cel in third line (3L) r/r LBCL.
Cautionary Note on Forward-Looking Statements for Allogene
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," “projects,” "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," “would,” “suggests,” "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: ALPHA3 being a pivotal trial; the pace, timing and extent to which Allogene may enroll patients in its clinical trials or release data from such trials; the timing and ability to progress the ALPHA3 trial; the potential for Allogene’s product candidates to be approved; the potential benefits of AlloCAR T products; the ability of our product candidates to treat various stages and types of cancers; Allogene’s ability to broaden patient access to CAR T therapy; the incidence, severity and manageability of side effects of allogeneic CAR T products; the extent to which our clinical trials will support regulatory approval of our product candidates; the potential for off-the-shelf CAR T products; our ability to deliver cell therapy on-demand, more reliably, and at greater scale to more patients. Various factors may cause material differences between Allogene’s expectations and actual results, including, risks and uncertainties related to: our product candidates are based on novel technologies, which makes it difficult to predict the time and cost of product candidate development and obtaining regulatory approval; the extent to which the
Allogene’s investigational oncology products utilize TALEN® gene-editing technology pioneered and owned by Cellectis. ALLO-501 and cemacabtagene ansegedleucel (previously known as ALLO-501A) are anti-CD19 AlloCAR T™ investigational products being developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. Servier grants to Allogene exclusive rights to ALLO-501 and cemacabtagene ansegedleucel in the U.S.
AlloCAR T™ is a trademark of Allogene Therapeutics, Inc.
PhasED-Seq™ is a trademark of
Foresight Contact:
press@foresight-dx.com
Allogene Media/Investor Contact:
EVP, Chief Corporate Affairs & Brand Strategy Officer
Christine.Cassiano@allogene.com
Additional Allogene Media Contacts:
Leslie.Bryant@allogene.com
Madeleine.Goldstein@allogene.com
i Tilly H, Morschhauser F, Sehn LH, Friedberg JW, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022;386(4):351-363
ii Kurtz, D.M., Soo, J.,
Roschewski M, Lindenberg L, Mena E, et al. Blood. 2023;142(Supplement 1):192-192. doi:10.1182/blood-2023-180007
iii Kurtz, D.M., Soo, J.,
iv Park JH, Rivière I, Gonen M, Wang X, Sénéchal B, Curran KJ, Sauter C, Wang Y, Santomasso B, Mead E, Roshal M, Maslak P, Davila M, Brentjens RJ, Sadelain M. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. N Engl J Med. 2018
Wudhikarn K, Tomas AA, Flynn JR, Devlin SM, Brower J, Bachanova V, Nastoupil LJ, McGuirk JP, Maziarz RT, Oluwole OO, Schuster SJ, Porter DL, Bishop MR, Riedell PA, Perales MA. Low toxicity and excellent outcomes in patients with DLBCL without residual lymphoma at the time of CD19 CAR T-cell therapy. Blood Adv. 2023 Jul 11;7(13):3192-3198. doi: 10.1182/bloodadvances.2022008294. PMID: 36355838; PMCID: PMC10338201
Source: Allogene Therapeutics, Inc.
Source: Foresight Diagnostics