TERN-701 Earns FDA Breakthrough Therapy Designation in Ph+ CML

The FDA has granted breakthrough therapy designation to the investigational BCR::ABL1 inhibitor TERN-701 as a treatment for adults with Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) in chronic phase following at least 2 prior tyrosine kinase inhibitors (TKIs), according to a press release from the developer, Terns Pharmaceuticals.¹

Developers designed TERN-701 as a highly selective, orally available allosteric BCR::ABL1 inhibitor with a potentially best-in-disease profile. The agent’s design may meaningfully improve upon the safety, efficacy, and convenience of prior anti-CML therapies.

Supporting data for the designation came from the ongoing phase 1/2 CARDINAL trial (NCT06163430) evaluating TERN-701 among patients with CML who received at least 1 prior TKI. Investigators previously highlighted findings from the CARDINAL trial at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition.²

How effective and safe was TERN-701 in the CARDINAL trial?

Among the evaluable patients who received TERN-701 at the recommended phase 2 dose of 320 mg once daily (n = 30), the agent produced a 24-week major molecular response (MMR) rate of 80% (95% CI, 61.4%-92.3%). Regarding patients who entered the study without an existing MMR (n = 24), data showed an MMR rate of 75% (95% CI, 53.3%-90.2%), and among those with an existing MMR (n = 6), the MMR rate was 100% (95% CI, 54.1%-100.0%).

Among 63 patients who received TERN-701 across all dose levels, any-grade treatment-emergent adverse effects (TEAEs) occurred in 81% of the population. Additionally, 32% experienced grade 3 or higher TEAEs. Investigators reported no dose-limiting toxicities (DLTs) during the dose-escalation portion of the study.

The most common AEs included diarrhea (21%), headaches (19%), nausea (19%), thrombocytopenia (16%), fatigue (14%), and neutropenia (13%). The most common grade 3 or higher toxicities included thrombocytopenia (8%), neutropenia (8%), and anemia (2%).

“There remains an urgent need for CML treatments that offer improved efficacy, safety, and tolerability over current therapies,” Scott Harris, chief development and operations officer at Terns Pharmaceuticals, stated in the press release.¹ “This designation from the FDA supports the significant potential of TERN-701 to be a best-in-disease therapy for patients with CML and offer substantial improvement based on the faster, deeper responses compared to prior TKIs and encouraging safety and tolerability profile observed to date.”

How was the CARDINAL trial designed?

Investigators of the open-label, ongoing CARDINAL trial first assessed TERN-701 at 4 dose levels––160 mg, 320 mg, 400 mg, and 500 mg once daily––as part of the dose-escalation phase.³ For the dose-expansion portion of the study, patients were assigned to receive the agent at 320 mg or 500 mg.

The trial’s end points included the incidence of DLTs, serious AEs, and AEs in part 1. End points in part 2 of the trial included the complete hematologic response rate, molecular response rate, and best categorical shit in BCR-ABL1 transcript levels from baseline.

Patients 18 years and older with an ECOG performance status of 0 to 2, a confirmed diagnosis of BCR-ABR1–positive CML in chronic phase, and prior treatment with at least 1 TKI plus treatment failure, suboptimal response, or treatment intolerance were eligible for enrollment on the trial. Having adequate organ function per local laboratory assessment was another requirement for study entry; patients were permitted to enroll if they had prior treatment with asciminib (Scemblix). Those who had completed previous anticancer therapy without resolution of any associated clinically significant toxicity to grade 2 or lower were ineligible for enrollment.

References

1. Terns Pharmaceuticals announces FDA breakthrough therapy designation granted to TERN-701 for certain patients with chronic myeloid leukemia. News release. Terns Pharmaceuticals, Inc. April 27, 2026. Accessed April 27, 2026. https://tinyurl.com/ypwrfyds
2. 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. 2025;146(suppl 1):901. doi:10.1182/blood-2025-901
3. A phase 1/​2 clinical study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TERN-701 in participants with chronic myeloid leukemia (CARDINAL) (CARDINAL). ClinicalTrials.gov. Updated January 12, 2026. Accessed April 27, 2026. https://tinyurl.com/jyket6fp