FDA Clears IND for TERN-701 for Chronic Myeloid Leukemia

The FDA has cleared an investigational new drug application for TERN-701 as a treatment for patients with chronic myeloid leukemia (CML), according to a press release from Terns Pharmaceuticals.

The safety, tolerability, efficacy, and pharmacokinetics of TERN-701 are set to be evaluated as part of the global phase 1 CARDINAL study (NCT05367700). The oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKIs) was created to go after the BCR-ABL myristoyl pocket, which is seen in the development of CML. The agent’s design could potentially resolve any possible issues involving active site TKIs such as off-target activity and lack of effectiveness vs active site resistance mutations.

A phase 1 study will evaluate TERN-701’s safety, efficacy, and pharmacokinetics in a population diagnosed with chronic myeloid leukemia.

Overall, investigators believe that TERN-701 could remedy the challenges presented with active-site TKIs by producing better tumor suppression via robust anti–BCR-ABL activity; this includes several mutations and improvements in safety.

Investigators expect to see the trial begin in the second half of 2023 and have the first potential topline data readout in 2024.

“Allosteric BCR-ABL inhibitors comprise a novel class of therapy for CML that has been shown to have superior efficacy and improved safety compared to active-site inhibitors in prior studies,” Emil Kuriakose, MD, chief medical officer of oncology at Terns Pharmaceuticals, said in the press release. “We are particularly pleased with our phase 1 trial design for TERN-701 as it will recruit [patients with] CML who experienced treatment failure on at least one prior second-generation TKI. This will allow us to offer a novel investigational allosteric inhibitor to [patients with] CML in as early as their second line of therapy, where there are currently no approved allosteric inhibitors.”

The multicenter, open-label CARDINAL study will include 2 parts. The first part has a dose escalation design in which TERN-701 will be examined in a population of 24 to 36 adult patients diagnosed with CML who will be included in 1 to 5 dose cohorts. Part 2 consists of a dose expansion design in which investigators will examine the recommended dose from the first part of the study.

The study’s primary end point is maximum tolerated dose in the dose escalation phase and major cytogenetic response in part 2. Secondary end points include safety, hematologic response, molecular response, cytogenetic response, event-free survival, progression-free survival, and overall survival.

To be included on the study, patients are required to have disease that’s in chronic phase and confirmed BCR-ABL or Philadelphia chromosome positivity. Moreover, patients need to have experienced treatment failure or poor response to a minimum of 1 second-generation TKI such as nilotinib (Tasigna), dasatinib (Sprycel), or bosutinib (Bosulif). Those who appeared intolerant to previous treatment with a TKI such as asciminib (Scemblix) were eligible to enroll.

Additional inclusion criteria include an ECOG performance status of 0 to 2, a life expectancy of 12 weeks or more, and being 18 years or older but younger than 75 years.

Those with acquired CCyR that is not lost, progression to acute phase or blast phase disease, or obtained CHR or no evidence of disease in the peripheral blood were not able to enroll on the study. Additionally, those who have been previously treated with a BCR-ABL1 TKI allosteric inhibitor, have impaired cardiac function, a history of acute pancreatitis within 1 year of the study initiation or a history of chronic pancreatitis, or any severe uncontrolled systemic diseases were not able to enroll on the study.

“We are excited to continue the clinical development momentum of TERN-701, which we believe can offer a valuable alternative to the only FDA-approved allosteric BCR-ABL TKI for CML,” Kuriakose concluded.

Reference

Terns Pharmaceuticals announces global phase 1 clinical trial design of TERN-701 for the treatment of chronic myeloid leukemia. News release. Terns Pharmaceuticals. October 16, 2023. Accessed October 24, 2023. https://bit.ly/3rUzTBO