David Andorsky, MD, Rocky Mountain Cancer Centers, Boulder, Colorado, presented early results from the phase 1/2 CARDINAL study which evaluated TERN-701, an allosteric BCR::ABL1 inhibitor, in previously treated chronic myeloid leukemia (CML) at the 2025 ASH Annual Meeting & Exposition.

Among 55 patients, TERN-701 demonstrated encouraging efficacy with a 75% major molecular response rate at 24 weeks and was well-tolerated, with mostly mild adverse events such as diarrhea, headache, and fatigue. 

Dr Andorsky concluded, “early data for this molecule appear to be showing that it's very well-tolerated. It appears to be highly efficacious in this patient population.”

Transcript:

Good afternoon. My name is Dr David Andorsky. I'm a hematologist practicing in Boulder, Colorado at the Rocky Mountain Cancer Centers and I'm a member of the Sarah Cannon Research Institute. I'm a co-author on the CARDINAL study, which is looking at early data from the TERN-701 compound for the treatment of chronic myeloid leukemia. I'm happy to share a little bit about the results we're presenting tomorrow afternoon at this year's ASH in Orlando.

CML is a disease that's undergone a huge transformation in the past 15 or 20 years with the introduction of tyrosine kinase inhibitors (TKI), which have converted it from a disease that people needed a bone marrow transplant for to one that's very well-controlled with oral medication. But we're always looking to move the bar forward, so TERN-701 is the latest entry in trying to improve treatment for our patients with this disease.

This study is a phase 1/2 study looking at TERN-701. This is an allosteric inhibitor of the BCR::ABL1 protein. In contrast to most of the other FDA approved tyrosine kinase inhibitors, which bind to the ATV binding site, this molecule binds allosterically to a different location on the BCR::ABL1 protein. It's similar in structure to asciminib, or Scemblix, which is approved last year for first line treatment of CML. This study looked at 55 patients so far treated in the phase 1/2 portion with a dose escalation from 116 milligrams daily of TERN-701 to 1 up to 500 milligrams. On the basis of those data, we selected 500 and 320 milligrams as the recommended phase 2 doses.

Now the study is in a randomized phase 2 study looking at comparing those 2 dose levels. These were patients that had all received at least one prior treatment for CML. The median, I believe was 3. The drug appears to be very well tolerated based on these early data. Virtually all the side effects were grade 1 and grade 2. Things like diarrhea, headache and fatigue occurred maybe 15 or 20% of the time. Only 1 patient discontinued treatment due to adverse events, which speaks a lot to the tolerability of this medication.

In terms of efficacy, we are presenting data on the 24-week major molecular response (MMR) rate, which is a PCR less than 0.1%. That was achieved in 75% of patients in the study, which again compares very favorably with other agents in this field, particularly in patients that have received multiple prior lines of therapy.

In conclusion, early data for this molecule appear to be showing that it's very well-tolerated. It appears to be highly efficacious in this patient population. We look forward to adding more patients to the study and presenting additional efficacy data at later congresses.

Thank you for your attention.

Source:

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. Dec 6-9, 2025; Orlando, FL. Abstract: 901