FDA Grants Breakthrough Therapy Designation to TERN-701 in Ph-Positive Chronic Myeloid Leukemia

Clinical Summary: 

• Based on data from the phase 1/2 CARDINAL study, the FDA has granted breakthrough therapy designation to TERN-701, a novel allosteric BCR::ABL1 inhibitor, for heavily pretreated adult patients with Ph-positive chronic myeloid leukemia who do not harbor a T315I mutation.
• TERN-701 demonstrated a 75% cumulative major molecular response rate by 24 weeks among evaluable patients, with durable responses and no loss of MMR at analysis. The safety profile was favorable, with no dose-limiting toxicities and predominantly low-grade adverse events.
• TERN-701 shows promising activity in a heavily pretreated population with limited options and may offer a new treatment approach for patients with CML who have progressed on prior TKIs.

Based on data from the phase 1/2 CARDINAL study, the US Food and Drug Administration (FDA) has granted breakthrough therapy designation to TERN-701, a novel allosteric BCR::ABL1 inhibitor, for heavily pretreated adult patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) who do not harbor a T315I mutation.

In this open-label study, 55 patients with BCR::ABL1-positive CML who had received at least 1 prior second-generation tyrosine kinase inhibitor (TKI) were treated with TERN-701 across dose-escalation cohorts ranging from 160 mg to 500 mg in continuous 28-day cycles, followed by randomized dose expansion. Primary end points included safety, pharmacokinetics, and efficacy, with efficacy defined as cumulative major molecular response (MMR) by 24 weeks.

At analysis, 48 patients remained on study treatment, with a median treatment duration of 4.5 months. Treatment discontinuations occurred due to disease progression (n = 4), adverse events (n = 1), and consent withdrawal or loss to follow-up (n = 2). At baseline, lack of efficacy was the reason for discontinuation of prior TKI therapy in 64% of patients, while 31% discontinued due to intolerance.

No dose-limiting toxicities were reported, and a maximum tolerated dose was not reached. The most frequently reported grade 1/2 treatment-emergent adverse events included diarrhea (22%), headache (18%), and nausea (16%). Grade ≥3 treatment-emergent adverse events occurred in ≤10% of patients and most commonly included neutropenia (7%) and thrombocytopenia (4%).

Among patients evaluable for efficacy (n = 32), 75% achieved or maintained MMR by 24 weeks. MMR was newly achieved in 64% of patients and maintained in 100% of those already in response. Responses were observed across clinically relevant subgroups, including patients with prior asciminib exposure and those who discontinued prior TKI therapy due to lack of efficacy. No patients experienced loss of MMR at the time of analysis.

“This designation from the FDA supports the significant potential of TERN-701 to be a best-in-disease therapy for CML patients and offer substantial improvement based on the faster, deeper responses compared to prior TKIs and encouraging safety and tolerability profile observed to date,” stated Scott Harris, chief development and operations officer, Terns. 

Sources: 

Terns Pharmaceuticals. Terns pharmaceuticals announces FDA breakthrough therapy designation granted to TERN-701 for certain patients with chronic myeloid leukemia. Accessed on April 29, 2026. https://ir.ternspharma.com/news-releases/news-release-details/terns-pharmaceuticals-announces-fda-breakthrough-therapy

Jabbour E, Hughes T, Van Etten R, et al. CARDINAL: A Phase 1 study of TERN-701, a novel investigational allosteric BCR::ABL1 inhibitor for patients with previously treated CML. Blood. Published online: November 3, 2025. doi:10.1182/blood-2025-901