Enliven Therapeutics, a clinical-stage biopharmaceutical company, has announced updated positive data from its Phase 1 clinical trial of ELVN-001 in patients with chronic myeloid leukemia (CML). The data, presented at the European Society of Hematology International Chronic Myeloid Leukemia Foundation (ESH-iCMLf) 26th Annual John Goldman Conference, demonstrated a cumulative major molecular response (MMR) rate of 44.4% (8/18) by 24 weeks in response-evaluable CML patients.
ELVN-001 is designed to specifically target the BCR-ABL gene fusion, the oncogenic driver for patients with CML. The Phase 1 trial (NCT05304377) is evaluating the safety and tolerability of ELVN-001, as well as determining the recommended dose for further clinical evaluation in TKI-resistant CML patients.
Efficacy and Safety Results
The updated data includes 39 patients across various dose levels, with 18 evaluable for molecular response by 24 weeks. Consistent with earlier 12-week results, ELVN-001 achieved a 44.4% cumulative MMR rate by 24 weeks. Notably, among TKI-resistant patients, ELVN-001 achieved a cumulative MMR rate of 41.7% (5/12) by 24 weeks, and among post-asciminib patients, the MMR rate was 40.0% (4/10) by 24 weeks.
According to Fabian Lang, M.D., from Goethe University Hospital Frankfurt, "ELVN-001 continues to show clinical benefit in heavily pretreated CML patients... We continue to see categorical improvements in molecular response, and the drug remains well-tolerated with an encouraging safety profile."
ELVN-001 continues to be well-tolerated, with no dose reductions reported. There have been no ≥ Grade 3 non-hematologic treatment-related adverse events (TRAE), and hematologic adverse events observed remain consistent with those observed with approved BCR::ABL1 TKIs.
Patient Demographics
As of the data cutoff date of June 25, 2024:
- 39 patients were enrolled in the Phase 1 trial across five dose levels (10 mg QD to 120 mg QD).
- The median treatment duration was 20 weeks.
- 69.2% of patients had ≥ 3 prior tyrosine kinase inhibitors (TKIs), and 25.6% had ≥ 5 prior TKIs.
- 53.8% of patients had received prior asciminib.
- 69.2% of patients had discontinued their last prior TKI due to lack of efficacy.
Potential Clinical Utility
Helen Collins, M.D., Chief Medical Officer of Enliven, stated, "With more patients enrolled and longer follow up, we continue to see anti-CML activity in a heavily pre-treated patient population that includes patients previously treated with asciminib... We believe the data demonstrate the potential clinical utility of ELVN-001 for patients across the full spectrum of the CML treatment paradigm."
Sam Kintz, Co-founder and Chief Executive Officer of Enliven, added, "We are encouraged to see stable and deepening responses between weeks 12 and 24 and clinical benefit for almost every patient we’ve enrolled. Most importantly… we continue to see an impressive safety and tolerability profile, which is especially important given the chronic nature of this disease."
About ELVN-001
ELVN-001 is a potent, highly selective small molecule kinase inhibitor designed to specifically target the BCR-ABL gene fusion. It was also 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.
