Terns Pharma Reports Positive Phase 1 CARDINAL Trial Data for TERN-701 in Chronic Myeloid Leukemia

Terns Pharmaceuticals has revealed promising early data from the dose escalation part of their ongoing Phase 1 CARDINAL study. This study is evaluating TERN-701 in patients with relapsed or refractory chronic myeloid leukemia (CML). TERN-701 is an oral, potent, allosteric BCR-ABL inhibitor designed for CML patients. The CARDINAL trial, which is happening on a global scale, is assessing the safety, pharmacokinetics (PK), and effectiveness of TERN-701 in CML patients who have been heavily pretreated.

Preliminary results from the Phase 1 trial show that TERN-701 has produced compelling molecular responses, even at the lowest dose levels, in patients who had high baseline BCR-ABL transcript levels. The safety profile of the drug has been encouraging, with no dose-limiting toxicities, adverse event-related treatment discontinuations, or dose reductions across three dose escalation groups. High levels of target coverage were achieved with once-daily dosing, and the completion of dose escalation and initiation of dose expansion are anticipated in the first half of 2025. More efficacy data, including long-term major molecular response (MMR) rates, are expected by the end of 2025.

As of late October 2024, 15 patients had been enrolled in the study across three different dose levels: 160mg, 320mg, and 400mg, with an overall median treatment duration of three months. These patients were heavily pretreated with a median of four prior tyrosine kinase inhibitors (TKIs), and most had received three or more TKIs. The results indicated that TERN-701 achieved significant decreases in BCR-ABL transcripts in patients with high baseline levels. Most patients remained on treatment, and the cumulative MMR rate was 50% in those without the T315i mutation, after three or more months of treatment.

Dr. Emil Kuriakose, Chief Medical Officer of Terns, highlighted the drug's clinical activity and safety profile, emphasizing its potential as a best-in-class treatment. Amy Burroughs, CEO of Terns, noted the clinical and operational success of the CARDINAL study, which enrolled patients in all four dose escalation cohorts within a year. The company aims to start dose expansion cohorts in the first half of 2025 and share further safety and efficacy data by late 2025.

Safety data from the study revealed no dose-limiting toxicities through the 400mg dose level and showed that no patients discontinued treatment due to adverse events. There were no Grade 3 or higher treatment-related adverse events, and the incidence of treatment-emergent hematologic adverse events was low. Additionally, there were no significant changes in liver and pancreatic enzymes, vital signs, or electrocardiograms.

Pharmacokinetic data indicated that TERN-701 showed linear PK with dose-proportional increases in exposure. At the 160mg and 320mg dose levels, the drug achieved average free drug concentrations significantly higher than those needed to inhibit the BCR-ABL signaling pathway effectively, suggesting robust pharmacodynamic effects at these clinical doses.

As of December 3, 2024, the CARDINAL study had enrolled 19 patients, including those in the 500mg cohort. Dose expansion is expected to begin in the first half of 2025, with additional efficacy data anticipated in the fourth quarter of 2025.