Senti Bio Determines Recommended Phase 2 Dose (RP2D) in Phase 1 Study of SENTI-202 for the Treatment of Relapsed/Refractory Hematologic Malignancies, Including Acute Myeloid Leukemia

Core Insights - Senti Biosciences is progressing towards reporting topline data for its Phase 1 clinical trial of SENTI-202 by year-end, having confirmed the recommended Phase 2 dose (RP2D) for its CAR-NK cell therapy targeting relapsed/refractory hematologic malignancies, including acute myeloid leukemia (AML) [1][2][3] Group 1: Clinical Trial Details - The Phase 1 trial of SENTI-202 is enrolling adult patients with relapsed or refractory CD33 and/or FLT3 expressing hematologic malignancies at multiple sites in the U.S. and Australia [2] - The RP2D has been established as Schedule I, Dose Level 2, with a dosage of 1.5 x 10 CAR+ NK cells administered on Days 0, 7, and 14 of 28-day cycles following lymphodepleting chemotherapy [2] - The company anticipates reporting clinical data, including efficacy and durability, from the expansion cohort before year-end [2] Group 2: Clinical Outcomes - SENTI-202 was well-tolerated with no dose-limiting toxicities, and 2 of 3 patients in the preliminary RP2D cohort achieved a composite Complete Remission (cCR) [4] - Among the 7 best overall response evaluable patients, 5 achieved an overall response rate (ORR), and 4 achieved cCR, with all cCR patients being measurable residual disease negative [4] - The median duration of cCR has not been reached, with the longest durability reported at over 8 months [4] Group 3: Product Overview - SENTI-202 is designed as a first-in-class off-the-shelf therapy targeting CD33 and/or FLT3-expressing hematologic malignancies while sparing healthy bone marrow cells [6] - The therapy incorporates an OR GATE for activating signals, a NOT GATE for protective signals, and calibrated-release IL-15 to enhance cell persistence and activity [6] - The NK cells used in SENTI-202 are sourced from selected healthy adult donors, positioning it as a potential allogeneic off-the-shelf treatment for AML/MDS patients [6] Group 4: Market Context - AML is the most common type of acute leukemia in adults, with an estimated 20,800 new cases in the U.S. in 2024 and a five-year survival rate of approximately 30% [9] - Current treatment options for patients with relapsed/refractory AML are limited, with median overall survival typically around five months [9]