お知らせ • Jun 11
Enliven Therapeutics, Inc. Announces Updated Positive Data From Phase 1 Enable Clinical Trial And Alignment With FDA On Key Phase 3 Trial Design Components
Enliven Therapeutics, Inc. issued a press release announcing updated positive data from the Phase 1 ENABLE clinical trial evaluating ELVN-001 in patients with chronic myeloid leukemia (CML). On June 11, 2026, the Company announced updated positive data from the Phase 1 ENABLE clinical trial evaluating ELVN-001 in patients with CML and key outcomes from the Company's End-of-Phase 1 meeting with the U.S. Food and Drug Administration (the FDA). As of the cutoff date of March 10, 2026, 161 patients were enrolled in the ongoing Phase 1 trial across dose levels ranging from 10-240 mg daily. Most patients (76%) remain on study with a median treatment duration of 35 weeks. Patients enrolled were heavily pretreated, with 70% having received three or more prior unique tyrosine kinase inhibitors (TKIs) and 23% having received five or more unique TKIs. 62% of patients received prior asciminib, and these patients were more heavily pretreated than the overall trial population: 93% received three or more prior unique TKIs, and 34% received five or more unique TKIs. 8% of patients enrolled with mutations associated with resistance to allosteric inhibitors, increasing from 4% in Phase 1a to 11% in Phase 1b. Of the 90 patients enrolled in the Phase 1b, 78 had typical BCR::ABL1 transcripts and had at least one post-baseline transcript; 69 patients were evaluable for major molecular response (MMR) by 24 weeks. Additionally, of the 49 patients enrolled in the 80 mg once daily (QD) Phase 1b cohort, 37 had typical BCR::ABL1 transcripts and had at least one post-baseline transcript; 28 patients were evaluable for MMR by 24 weeks. Cohort (n = evaluable for MMR) Phase 1b: Overall MMR 54% (n=69), Achieved MMR 40% (n=53), Maintained MMR 100% (n=16); Phase 1b 80 mg QD Cohort: Overall MMR 61% (n=28), Achieved MMR 48% (n=21), Maintained MMR 100% (n=7). Deep Molecular Response (DMR) achievement rates were also encouraging. By 24 weeks, DMR was achieved in 22% of patients in the overall Phase 1b and 30% of patients in the 80 mg QD Phase 1b cohort. Response rates were higher in less heavily pretreated patients, and prior asciminib exposure did not meaningfully impact response rates. Achieved Response Rates by 24-weeks (n = evaluable for MMR): Prior number of unique TKIs: Phase 1b (n=69): 1-2: 55% (n=27), 3-4: 32% (n=26), 5+: 29% (n=16); Phase 1b post-asciminib (n=43): 1-2: 60% (n=6), 3-4: 28% (n=22), 5+: 29% (n=15). ELVN-001 was generally well-tolerated, consistent with its high selectivity. 6% of patients discontinued due to adverse events. The majority of treatment-emergent adverse events (TEAEs) were Grade 1 or 2. Grade 3 TEAEs were reported in 53/158 (34%) patients overall; with thrombocytopenia (6%), neutropenia (6%) and lipase elevation (6%) as the most common. At the biologically optimal dose of 80 mg QD (n=62), Grade 3 TEAEs were reported in 15/62 (24%) patients, with thrombocytopenia (6%) being the only Grade 3 TEAE reported in >5% of patients. 80 mg QD selected as the recommended dose for Phase 3 ENABLE-2 trial. ENABLE-2 is expected to enroll patients with CML previously treated with one or more TKIs, and to be randomized to receive either ELVN-001 or physician's choice of an ATP-competitive TKI. Additional details of the Phase 3 trial design are expected to be finalized following further discussions with the FDA, including at a planned End-of-Phase 2 meeting anticipated in the third quarter of 2026. ELVN-001 is a potent, highly selective, potentially best-in-class small molecule kinase inhibitor designed to specifically target the BCR::ABL1 gene fusion, the oncogenic driver for patients living with CML. Data presented at EHA are from the ongoing ENABLE Phase 1 clinical trial, which enrolled patients with CML that is relapsed, refractory or intolerant to available tyrosine kinase inhibitors (TKIs) (NCT05304377). The ENABLE study (NCT05304377) is a Phase 1 study of ELVN-001 in patients with previously treated CML. ENABLE is a dose escalation and expansion trial designed to evaluate safety and tolerability and to determine the recommended dose for further clinical evaluation of ELVN-001 in patients with CML with and without T315I mutations that is relapsed, refractory or intolerant to TKIs. Secondary endpoints include pharmacokinetics, MMR by central quantitative reverse transcriptase polymerase chain reaction, duration of MMR, BCR::ABL1 transcript levels and complete hematologic response. ELVN-001 is a potent, highly selective, potentially best-in-class small molecule kinase inhibitor designed to specifically target the BCR::ABL gene fusion, the oncogenic driver for patients with chronic myeloid leukemia. ELVN-001, a highly selective active-site TKI, has a mechanism of action that is complementary to allosteric BCR::ABL1 inhibitors, which may play an increasingly important role in the standard of care. ELVN-001 was designed to have activity against the T315I mutation, the most common BCR::ABL1 mutation, which confers resistance to nearly all approved TKIs, as well as activity against mutations known to confer resistance to allosteric BCR::ABL1 inhibitors.
