The U.S. Food and Drug Administration (FDA) has granted regenerative medicine advanced therapy (RMAT) designation to SENTI-202, Senti Biosciences‘ experimental cell therapy being developed for adults with hard-to-treat blood cancers, including acute myeloid leukemia (AML).
RMAT status aims to speed the development of cellular and engineered therapies that show early potential to address unmet needs in serious health conditions. It provides benefits such as closer collaboration with the FDA during the development process and eligibility for accelerated approval.
“This significant FDA designation validates both the tremendous need for better treatments for [relapsed or refractory] AML and the promise of SENTI-202 to transform the therapeutic landscape for this notoriously aggressive cancer,” Timothy Lu, MD, PhD, co-founder and CEO of Senti, said in a company press release.
RMAT designation reflects early clinical activity
The designation was based on data from a Phase 1 clinical trial (NCT06325748) showing that 42% of evaluable patients with relapsed or refractory AML treated at the recommended Phase 2 dose achieved complete remission or complete remission with partial hematologic recovery (CR/CRh).
The results, titled “Promising Results from an Ongoing Phase I Multicenter Study of SENTI-202, a First-In-Class, CD33 AND/OR FLT3 & NOT endomucin (EMCN), Selective Off-the-Shelf Logic Gated CAR NK Cell Therapy in Adults with Relapsed/Refractory Acute Myeloid Leukemia (R/R AML),” were presented at the American Society of Hematology (ASH) Annual Meeting, held this month in Orlando, Florida.
Acute Myeloid Leukemia (AML) is a rapidly progressing blood cancer that occurs when immature white blood cells multiply rapidly, replacing healthy cells and leading to anemia (low levels of red blood cells), infections, and bleeding issues.
SENTI-202 works by collecting natural killer (NK) cells, a type of immune cell that can destroy cancer cells, from a healthy donor and engineering them to express a chimeric antigen receptor (CAR). This receptor guides the cells to bind two target proteins, CD33 and FLT3, which are found on some blood cancer cells. The CAR is also designed to prevent NK cells from attacking healthy cells.
The therapy is being developed as an off-the-shelf therapy, which can be cryopreserved and used as needed.
Phase 1 study evaluates SENTI-202 in relapsed or refractory AML
The Phase 1 trial tested SENTI-202 in 20 people with relapsed or refractory AML, with a median age of 49, who received one of two dose levels: 1 billion cells (six patients) or 1.5 billion cells (14 patients). Prior to treatment, participants underwent a lymphodepletion regimen using two chemotherapy medications to reduce their own immune cells and make room for the infused treatment cells.
Compared with those who received the lower dose, patients who received the higher dose had undergone more prior treatments (two vs. one) and included a higher proportion of individuals who had not responded to their most recent treatment before receiving SENTI-202 (79% vs. 17%). Additionally, these patients responded after a single treatment cycle, and this dose was selected as the recommended dose for a Phase 2 trial.
Half of the patients who received the highest dose achieved an overall response, with 42% reaching complete remission or complete remission with partial hematologic recovery. Among patients who achieved composite complete remissions, the estimated median duration of response was 7.6 months.
This significant FDA designation validates both the tremendous need for better treatments for [relapsed or refractory] AML and the promise of SENTI-202 to transform the therapeutic landscape for this notoriously aggressive cancer.
In all patients who experienced a complete remission, as well as in about 80% of all responses, measurable residual disease was not detected.
Treatment was generally well tolerated, with most SENTI-202-related adverse events being mild to moderate in severity. The most common of those were fever, chills, low blood pressure, and oxygen deficiency. Serious side effects, such as fever, low blood cell counts, and abdominal pain, were reported, but were mostly attributed to the lymphodepletion regimen rather than to SENTI-202 itself.
Kanya Rajangam, MD, PhD, Senti’s chief medical officer, said: “We view the FDA’s decision to grant RMAT and Orphan Drug designations to SENTI-202 as major milestones for the AML patient community and we look forward to working with regulators to develop this potentially first-in-class treatment as quickly as possible and to accelerate a paradigm shift in how we treat other difficult cancers.”
SENTI-202 was also recently granted FDA orphan drug designation for the treatment of relapsed/refractory blood cancers, including AML. The designation aims to encourage the development of therapies to treat rare diseases.
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