ELVN-001 Appears Safe and Effective in Relapsed/Refractory CML

ELVN-001 generated prolonged signals of clinical activity with a tolerable safety profile in patients with chronic myeloid leukemia (CML) who have progressed on, are intolerant to, or are not candidates for other available and active treatment options, according to updated findings from the ongoing phase 1 ELVN-001-101 trial (NCT05304377) presented at the European Society of Hematology International Chronic Myeloid Leukemia Foundation 26th Annual John Goldman Conference (ESH-iCMLf).¹

ELVN-001 is a potent and highly selective small molecule inhibitor that is designed to target the BCR-ABL gene fusion, which is the oncogenic driver of CML.

The updated dataset included 39 patients who received various dose levels of the agent as of a data cutoff date of June 25, 2024, 18 of whom were evaluable for molecular response at 24 weeks. Among evaluable patients, all of whom had typical transcripts and lacked T315I mutations, the cumulative major molecular response (MMR) rate was 44.4%, and the median duration of treatment was 20 weeks. Most patients remained on the study by the data cutoff date, and no patients underwent dose reductions.

“I [was] happy to present the updated ELVN-001 phase 1 data…at ESH-iCMLf. ELVN-001 continues to show clinical benefit in heavily pretreated [patients with] CML,” presenting study author Fabian Lang, MD, of Goethe University Hospital in Frankfurt, Germany, stated in a news release. “I am encouraged that the initial clinical profile presented in April [2024] continues to hold, even as patient numbers and the median duration of exposure increased. We continue to see categorical improvements in molecular response, and the drug remains well tolerated with an encouraging safety profile. Despite recent advancements in the CML treatment paradigm, there continues to be a need for more efficacious and better tolerated active-site TKIs, especially for patients who have [progressed on] treatment with allosteric inhibitors. I remain excited to see the progress of ELVN-001 as the trial continues.”

The phase 1 dose-escalation and -expansion ELVN-001-101 trial is evaluating the safety and tolerability of ELVN-001, as well as the recommended dose for further clinical evaluation, in patients with CML that is relapsed, refractory, or intolerant to TKIs, regardless of T315I mutation status. Safety serves as the trial’s primary end point. Secondary end points include pharmacokinetics, MMR, duration of MMR, BCR::ABL1 transcript levels, and complete hematologic response.

In ELVN-001-101, patients received ELVN-001 across 5 dose levels ranging from 10 mg once daily to 120 mg once daily. In total, 69.2% of patients had received at least 3 prior TKIs, and 25.6% of patients had received at least 5 prior TKIs. Additionally, 53.8% of patients had received prior asciminib (Scemblix), and 69.2% of patients had discontinued their most recent TKI because of a lack of efficacy.

Preliminary efficacy data released in April 2024 showed that ELVN-001 produced a cumulative MMR in 44% of 16 patients who were evaluable for efficacy at 12 weeks.² Among TKI-resistant patients and patients who had received prior asciminib, 40% and 44%, respectively, achieved MMR by 12 weeks.

All 16 patients who were previously evaluated for efficacy at 12 weeks experienced stable or deepening responses between weeks 12 and 24.¹ Among TKI-resistant patients, patients who had received prior asciminib, and patients who were not in MMR at baseline, 41.7%, 40.0%, and 23.1%, respectively, achieved MMR by 24 weeks.

The maximum tolerated dose of ELVN-001 has not been identified. No patients who have received the agent at doses of 40 mg or higher have undergone treatment discontinuations because of treatment-emergent adverse effects (TEAEs). No grade 3 or higher non-hematologic treatment-related adverse effects (TRAEs) have been observed. Furthermore, more than 14% of patients had no specific non-hematologic TEAEs, and over 11% of patients did not experience any TRAEs.

“We are excited by the continued advancement of the phase 1 ELVN-001 trial, and we remain confident in ELVN-001’s potential to address the limitations of the available active-site TKIs,” Helen Collins, MD, chief medical officer of Enliven Therapeutics, added in the news release.¹ “With more patients enrolled and longer follow-up, we continue to see anti-CML activity in a heavily pretreated patient population that includes patients previously treated with asciminib. Additionally, ELVN-001’s safety profile remains consistent with its high selectivity, even with longer duration and more patients enrolled at higher dose levels. We believe the data demonstrate the potential clinical utility of ELVN-001 for patients across the full spectrum of the CML treatment paradigm.”

References

1. Enliven Therapeutics announces positive data update from phase 1 clinical trial of ELVN-001 in chronic myeloid leukemia. News release. Enliven Therapeutics, Inc. September 28, 2024. Accessed October 7, 2024. https://ir.enliventherapeutics.com/news-releases/news-release-details/enliven-therapeutics-announces-positive-data-update-phase-1
2. Enliven Therapeutics announces positive proof of concept data from phase 1 clinical trial of ELVN-001 in chronic myeloid leukemia. News release. Enliven Therapeutics, Inc. April 11, 2024. Accessed October 7, 2024. https://ir.enliventherapeutics.com/news-releases/news-release-details/enliven-therapeutics-announces-positive-proof-concept-data-phase