Enliven’s ELVN-001 achieved up to 61% major molecular response in pretreated chronic myeloid leukemia, with FDA endorsing an 80 mg once-daily dose and pivotal Phase 3 ENABLE-2 trial design.
Written By: Kirti Kumbahr, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Enliven Therapeutics presented updated results from the Phase 1 ENABLE trial (NCT05304377) of ELVN-001 in chronic myeloid leukemia (CML) at the European Hematology Association (EHA) 2026 Congress. Among 69 evaluable patients, ELVN-001 achieved a 54% overall major molecular response (MMR) rate, with 40% reaching MMR by 24 weeks.
In the 80 mg once-daily cohort, outcomes improved further, with a 61% overall MMR rate and 48% achieving MMR within 24 weeks. Deep molecular responses, a marker of deeper disease control, were achieved by 30% of patients in the 80 mg cohort by week 24.
Mechanism Targets Resistance Mutations
ELVN-001 is a highly selective ATP-competitive inhibitor of the BCR::ABL1 fusion protein, the oncogenic driver of CML. Unlike allosteric inhibitors, ELVN-001 binds the kinase active site and has demonstrated activity against the T315I mutation and other resistance-associated variants. This profile may address persistent challenges in CML management, where patients often cycle through multiple tyrosine kinase inhibitors (TKIs) because of resistance or intolerance.
Durable Responses Across Heavily Pretreated Patients
As of March 10, 2026, ENABLE had enrolled 161 patients, 70% of whom had received three or more prior TKIs, and 23% had received five or more. Prior asciminib exposure was reported in 62% of participants. Despite this heavily pretreated population, ELVN-001 delivered durable molecular responses.
Response rates were highest in patients treated earlier in the disease course. Among patients who had received one or two prior TKIs, overall MMR reached 67%, suggesting stronger activity when ELVN-001 is used earlier in the treatment sequence. Prior asciminib exposure did not meaningfully diminish response rates, underscoring ELVN-001’s potential utility across multiple treatment settings.
Favorable Safety Profile Supports Long-Term Use
Safety findings were consistent with ELVN-001’s selective mechanism. Most adverse events were Grade 1 or 2, and only 6% of patients discontinued treatment because of toxicity. Grade 3 or higher events occurred in 34% of patients overall, most commonly thrombocytopenia, neutropenia, and lipase elevation, each reported in 6% of patients.
At the proposed Phase 3 dose of 80 mg once daily, Grade 3 or higher adverse events were reduced to 24%, with thrombocytopenia the only event occurring in more than 5% of patients. Median treatment duration was 35 weeks, and 76% of patients remained on therapy at the data cutoff.
Clinical Implications
Dennis Kim, M.D., of the Princess Margaret Cancer Centre said the updated ENABLE data showed meaningful molecular responses across multiple lines of therapy in a heavily pretreated CML population, including patients who had previously failed approved treatments. He also highlighted ELVN-001’s favorable safety and tolerability profile.
Helen Collins, M.D., Enliven’s Chief Medical Officer, noted that responses were strongest in earlier-line patients and remained consistent regardless of prior asciminib exposure. She added that FDA alignment on the 80 mg once-daily dose and planned Phase 3 population marks an important step toward initiating the ENABLE-2 study later this year.
FDA Alignment and Phase 3 ENABLE-2 Trial
Following its End-of-Phase 1 meeting, the FDA endorsed Enliven’s proposed 80 mg once-daily dose and the inclusion of patients previously treated with one or more TKIs in the pivotal ENABLE-2 trial. The randomized Phase 3 study, expected to launch in the second half of 2026, will compare ELVN-001 with physician’s choice of an ATP-competitive TKI.
An End-of-Phase 2 meeting is planned for the third quarter of 2026 to finalize trial design details. If successful, ENABLE-2 could establish ELVN-001 as a new treatment option for patients with relapsed, refractory, or intolerant CML following prior TKI therapy.
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About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.