FDA Clears IND of TERN-701 for Chronic Myeloid Leukemia

• TERN-701 is an oral, potent, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) that aims to target the BCR-ABL myristoyl pocket.

• An ongoing phase 1 trial in China evaluating TERN-701 supports the study design of the upcoming phase 1 CARDINAL trial.

• CARDINAL will evaluate the safety, pharmacokinetics (PK), and efficacy of TERN-701 in patients with previously treated chronic myeloid leukemia (CML).

The FDA has cleared the investigational new drug application and the design of the phase 1 CARDINAL trial, evaluating the safety, tolerability, PK, and efficacy of TERN-701 in patients with CML, according to Terns Pharmaceuticals, Inc.¹

TERN-701 is an allosteric BCR-ABL TKI which targets the BCR-ABL myristoyl pocket. The oral, potent TKI aims to combat the challenges and limitations seen with active-site TKIs, and has the goal of achieving improved tumor suppression through a combination of potent activity against BCR-ABL. This includes a broad range of mutations and improved safety and tolerability profiles.²

The design cleared by the FDA utilizes insights from an ongoing phase 1 trial in China which supports a starting dose that appears safe and clinically active, based on emerging early clinical data.¹

presence of abundant mast cells: © catalin - stock.adobe.com

“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. We are particularly pleased with our phase 1 trial design for TERN-701 as it will recruit chronic CML patients who experienced treatment failure on at least one 1 prior second-generation TKI. This will allow us to offer a novel investigational allosteric inhibitor to CML patients in as early as their second line of therapy, where there are currently no approved allosteric inhibitors,” said Emil Kuriakose, MD, chief medical officer-oncology at Terns Pharmaceuticals, in a press release.

In the global, multicenter, open-label, 2-part, phase 1 CARDINAL trial, investigators will evaluate the safety, PK, and efficacy of TERN-701 in patients with previously treated CML across the United States, Europe, and other Terns global territories. The overall goal of the study is to determine the optimal dose of TERN-701 to move forward to a potential pivotal trial for patients with chronic phase CML.

The study will consist of 2 parts, with part 1 being the dose-escalation portion of the trial assessing once-daily TERN-701 monotherapy, and part 2 as the dose-expansion portion which will randomize patients to once-daily treatment with 1 of 2 doses of TERN-701 to be selected based on the findings from part 1.

In part 1, approximately 24-36 adult patients with CML are being enrolled in up to 5 dose cohorts if they have chronic-phase CML with confirmed BCR-ABL. Patients must also have a history of treatment failure or suboptimal response to at least 1 second generation TKI, and patients intolerant to prior TKI treatment are eligible for enrollment. The starting dose being given to patients in this portion of the study is 160 mg once-daily (QD) with dose escalations as high as 500 mg QD and the option to explore a lower dose of 80 mg QD.

The primary end points being evaluated in part 1 include the incidence of dose-limiting toxicities (DLTs) during the first treatment cycle, safety, and tolerability. Secondary end points being explored are PK and efficacy assessments, including hematologic and molecular responses as measured by the change from baseline in BCR-ABL transcript levels.

Part 2 plans to enroll approximately 40 patients and will assess the primary end point of efficacy, measured by hematologic and molecular responses, and secondary end points of safety, tolerability and PK.

Global site identification and trial start-up activities are ongoing, and the first patient to be screened is expected in December 2023. Initiation of the CARDINAL trial is expected for the second half of 2023. Potential interim top-line readouts from initial cohorts may be reported in 2024.

“Importantly, we were able to leverage emerging early clinical data from the ongoing phase 1 trial in China conducted by our partner, Hansoh, to inform the dose selection for the CARDINAL Trial. This enables us to accelerate our study and the overall development of this molecule, while enhancing our ability to best dose optimize TERN-701 for patients with CML. 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. We are well-positioned to report initial data from this global phase 1 trial in the second half of 2024,” added Kuriakose, in a press release.

REFERENCES:

1. Terns Pharmaceuticals announces global phase 1 clinical trial design of TERN-701 for the treatment of chronic myeloid leukemia. News release. Terns Pharmaceuticals, Inc. October 16, 2023. Accessed October 16, 2023. https://tinyurl.com/4hsc2z95

2. Our programs. Terns Pharmaceuticals, Inc. Accessed October 16, 2023. https://www.ternspharma.com/our-programs