Enliven Therapeutics reaches FDA alignment on the Phase 3 ENABLE-2 trial of relcobatinib in previously treated CML, with initiation planned for 2026.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Enliven Therapeutics announced on October 6, 2026, that it has reached agreement with the FDA on the final design of ENABLE-2, its planned pivotal Phase 3 clinical trial of relcobatinib in patients with previously treated CML.
The regulatory milestone establishes the framework for the company’s next-stage clinical evaluation of the investigational therapy, with trial initiation expected before year-end.
Relcobatinib, formerly identified as ELVN-001, is the nonproprietary name adopted by the United States Adopted Names (USAN) Council. Enliven describes relcobatinib as a potent and highly selective small-molecule kinase inhibitor designed to specifically target the BCR::ABL1 gene fusion, the oncogenic driver of chronic myeloid leukemia CML.
The company is developing relcobatinib as an ATP-competitive inhibitor and plans to evaluate its potential as a best-in-class therapy in CML.
ENABLE-2 to Evaluate Relcobatinib in Previously Treated CML
ENABLE-2 is planned as a randomized Phase 3 trial in the second-line and later treatment setting for adults with CML who have previously received one or more tyrosine kinase inhibitors (TKIs).
The study is expected to enroll approximately 450 patients. Participants will be randomized in a 1:1 ratio to receive either relcobatinib at a dose of 80 mg once daily or an investigator-selected second-generation TKI.
The specified comparator therapies are dasatinib, nilotinib, and bosutinib.
The primary endpoint is major molecular response (MMR) at Week 24, while MMR at Week 96 has been selected as the key secondary endpoint. The study will therefore use molecular response as its principal efficacy measure.
Trial Designed to Assess Statistical Superiority
According to Enliven, the planned sample size of approximately 450 patients is designed such that an improvement in the MMR rate of at least 10 percentage points compared with the control arm would be sufficient to demonstrate statistical superiority.
The company considers a 10-percentage-point improvement to represent a clinically meaningful difference compared with the second-generation TKIs included in the control group.
Importantly, this statistical objective is a feature of the planned trial design and does not represent demonstrated efficacy. ENABLE-2 has not yet begun, and no comparative efficacy conclusion can be drawn until results from the randomized Phase 3 study become available.
FDA Alignment Builds on Earlier Development Discussions
The October FDA alignment follows earlier regulatory discussions in June 2026. At that time, Enliven reported alignment with the FDA on 80 mg once daily as the recommended Phase 3 dose and on the second-line-or-later patient population for ENABLE-2.
The company subsequently continued discussions with the FDA to finalize additional elements of the pivotal trial design. The October announcement now establishes the final design for the planned Phase 3 study.
This progression provides a defined framework for moving relcobatinib from the ongoing Phase 1 development program into pivotal testing.
Trial Expected to Begin Before End of 2026
Enliven remains on track to initiate ENABLE-2 before the end of 2026. The planned study will provide a randomized comparison of relcobatinib with investigator-selected second-generation TKIs in adults with previously treated CML.
The transition to Phase 3 testing represents the next clinical development step for relcobatinib. The approximately 450-patient population, 1:1 randomization, 80 mg once-daily relcobatinib regimen, active TKI comparator group, and predefined molecular-response endpoints establish the framework for evaluating the investigational therapy in the second-line and later treatment setting.
The FDA alignment provides Enliven with a defined regulatory framework for advancing the planned pivotal trial. ENABLE-2 is intended to evaluate whether relcobatinib can achieve a statistically superior MMR rate compared with the selected second-generation TKI control arm and generate pivotal clinical evidence to support its subsequent regulatory development.
For now, relcobatinib remains an investigational therapy, and its potential clinical benefit cannot be established from the planned study design alone. The initiation and subsequent results of ENABLE-2 will provide the evidence needed to assess its efficacy and safety in previously treated CML.
Reference
Enliven Therapeutics Announces FDA Alignment on ENABLE-2 Phase 3 Trial Design for Relcobatinib (ELVN-001) in Previously Treated Chronic Myeloid Leukemia, Enliven, 06 October 2026
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.