お知らせ • Apr 24
PureTech Reports Positive Topline Data from Phase 1b Trial of LYT-200 in Relapsed/Refractory (R/R) High-Risk (HR) Myelodysplastic Syndrome (MDS) and R/R Acute Myeloid Leukemia (AML)
PureTech Health plc announced positive topline data from the completed Phase 1b clinical trial of LYT-200, a first-in-class, fully human anti-galectin-9 monoclonal antibody, in heavily pretreated patients with relapsed/refractory high-risk myelodysplastic syndrome and relapsed/refractory acute myeloid leukemia. Based on the results, PureTech’s Founded Entity, Gallop Oncology, has selected a recommended Phase 2 dose and intends to engage with the U.S. Food and Drug Administration to discuss the design of a subsequent trial that could potentially support registration of LYT-200 in relapsed/refractory high-risk myelodysplastic syndrome. The completed Phase 1b trial (NCT05829226), conducted across nine U.S. sites, evaluated LYT-200 both as a monotherapy and in combination regimens in two heavily pretreated patient populations. The study included dose escalation of monotherapy LYT-200, followed by dose escalation of LYT-200 in combination with a hypomethylating agent (azacitidine or decitabine) in patients with relapsed/refractory high-risk myelodysplastic syndrome and with venetoclax and a hypomethylating agent in relapsed/refractory acute myeloid leukemia. LYT-200 demonstrated a favorable and consistent safety profile across all cohorts and dose levels studied (N=101), with no dose-limiting toxicities, infusion-related reactions, LYT-200 dose reductions, or LYT-200-related serious adverse events, discontinuations, or deaths. Importantly, no overlapping or additive toxicities were observed when LYT-200 was combined with a hypomethylating agent or venetoclax/hypomethylating agent. Six patients at one study site reported experiencing hematology/chemistry-related Grade 3 or 4 adverse events attributed as possibly related or related to LYT-200 in the combination arm at the recommended Phase 2 dose. The reported adverse events consisted of decreased levels of platelets, white blood cells, and neutrophils that were below the lower limit of normal physiological levels. The blood count deficits for some of the relevant patients were present at baseline prior to the administration of LYT-200 and are common occurrences in patients due to the underlying advanced myelodysplastic syndrome/acute myeloid leukemia, as well as in those receiving venetoclax/hypomethylating agent treatment. No other sites reported Grade 3 or greater adverse events related to LYT-200 treatment. Treatment with LYT-200 in combination with a hypomethylating agent in relapsed/refractory high-risk myelodysplastic syndrome patients and venetoclax/hypomethylating agent in relapsed/refractory acute myeloid leukemia patients demonstrated robust antileukemic activity, including complete responses, bridging to transplant, and durable clinical benefit. Across all efficacy-evaluable patients (n=11), the recommended Phase 2 dose (LYT-200 12mg/kg in combination with a hypomethylating agent) demonstrated a 27.3% complete response rate, 9.1% partial response rate, 9.1% marrow complete response rate, 45.5% overall response rate, and 18% conversion to transplant rate. Due to the number of patients alive at the time of study completion (>50%), the upper bound of overall survival could not be calculated; therefore, the median overall survival for this cohort of 6.4 months is not considered fully mature. Efficacy-evaluable patients had a median of 3 prior lines of therapy (range: 1-5), and all (100%) had previously been treated with a hypomethylating agent. Additionally, all patients had high-risk cytogenetics, which – coupled with prior exposure to treatment – suggests biologically aggressive, treatment-refractory disease with elevated risk of progression and poor clinical outcomes. Across all efficacy-evaluable patients (n=26), LYT-200 12mg/kg in combination with venetoclax/hypomethylating agent demonstrated a 30.8% composite complete response rate; responders included patients with mutations associated with venetoclax resistance, 7.7% partial response rate, 42.3% overall response rate, and 19.2% conversion to transplant rate. Due to the number of patients alive at the time of study completion (50%), the upper bound of overall survival could not be calculated; therefore, the median overall survival for this cohort of 8.2 months is not considered fully mature. Efficacy-evaluable patients had a median of 2 prior lines of therapy (range: 1-9), and 84.6% had previously been treated with venetoclax/hypomethylating agent. The systemic effects of LYT-200 were evaluated through pharmacodynamic analyses of peripheral blood mononuclear cells, a population of immune cells in the bloodstream that provides insight into how a treatment affects both the immune system and leukemic blast cells. These analyses suggest that LYT-200 engages complementary and potentially synergistic pathways directed at cancer cell killing and anti-cancer immune responses when combined with venetoclax and hypomethylating agent-based therapy, which may contribute to the clinical activity observed in patients with relapsed/refractory disease following hypomethylating agent and venetoclax/hypomethylating agent treatment, in myelodysplastic syndrome and acute myeloid leukemia, respectively. LYT-200 is a fully human IgG4 monoclonal antibody in development for the treatment of hematological malignancies. LYT-200 targets galectin-9, which is an important oncogenic driver and potent immunosuppressor in cancer, positioning it as a novel target for cancer therapy. LYT-200 has been granted Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration for the treatment of acute myeloid leukemia. Gallop Oncology was founded by and is currently wholly-owned by PureTech Health plc. Gallop is advancing a novel approach where efficacy, safety, and durability converge. Its lead candidate, LYT-200, is the most advanced candidate targeting galectin-9, an important oncogenic driver and potent immunosuppressor in cancer, offering a differentiated strategy to address some of the most challenging cancers.
