TERN-701 for Leukemia

(CARDINAL Trial)

Recruiting at 68 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Terns, Inc.

Must not be taking: Antineoplastics, Chemotherapy

Disqualifiers: Systemic therapy, Unresolved toxicity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests TERN-701, a new drug for chronic myeloid leukemia (CML), a type of blood cancer. Researchers aim to determine if TERN-701 is safe and effective for individuals whose previous treatments failed or caused issues. The trial consists of two parts: first, determining the right dose, and second, evaluating the effectiveness of these doses. Individuals previously treated for CML with other drugs but without success might be suitable for this study. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic antineoplastic therapy (cancer treatment) at least 7 days before starting TERN-701. This includes prior TKIs, interferon-alfa, therapeutic antibodies, and chemotherapy.

Is there any evidence suggesting that TERN-701 is likely to be safe for humans?

Research has shown promising safety results for TERN-701 in treating chronic myeloid leukemia (CML). Early studies indicate that patients generally tolerate TERN-701 well. Importantly, no severe side effects have emerged that would prevent increasing the dose, suggesting the treatment might be safe at various dose levels.

Additionally, TERN-701 has demonstrated a strong positive response in CML patients, which is encouraging. While the focus remains on safety, the lack of major unwanted side effects in early research is a positive sign for those considering joining a trial.

Every new treatment carries some risk. It is important to consult a healthcare professional to understand what this means personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leukemia?

TERN-701 is unique because it promises a novel approach to treating leukemia by potentially offering daily oral administration, which is more convenient than some existing treatments that require intravenous delivery. Researchers are excited about TERN-701 because it has a new mechanism of action that may target leukemia cells more effectively, improving patient outcomes. Additionally, TERN-701 is being studied at various dose levels to optimize its safety and efficacy, setting it apart from current standard therapies that might not offer such flexibility in dosing.

What evidence suggests that TERN-701 might be an effective treatment for chronic myeloid leukemia?

Research has shown that TERN-701 holds promise for patients with chronic myeloid leukemia (CML). In earlier studies, TERN-701 helped 75% of patients who were difficult to treat, which is impressive. Another study found that after 24 weeks, the response rate with TERN-701 was at least twice as high as in other studies. Additionally, TERN-701 significantly reduced levels of BCR-ABL, a cancer-causing protein, in patients without a specific mutation, achieving a 50% response rate after three months. These results suggest that TERN-701 could effectively manage CML. Participants in this trial will receive different doses of TERN-701 to further evaluate its safety and efficacy. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic myeloid leukemia who've had issues with previous treatments like intolerance or inadequate response. They should be relatively active (able to walk and do light activities), have their major organs working well, and not be in the advanced stages of leukemia.

Inclusion Criteria

My organs are working well, according to tests.

My leukemia is confirmed to be BCR-ABL1 positive in the chronic phase.

I have had a poor response or intolerance to targeted cancer therapy.

Exclusion Criteria

I haven't taken cancer drugs or been in a trial for at least 7 days.

My leukemia is in an advanced stage.

I still experience side effects from cancer treatment, but they are mild.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part 1 of the trial will evaluate sequential dose escalation cohorts of TERN-701 administered once daily.

28-day cycles

Visits on C1D1, C1D2, C1D8, C1D15, C1D16, and Day 1 of Cycles 2-7

Dose Expansion

Part 2 consists of randomized, parallel dose expansion cohorts of TERN-701 to evaluate efficacy and safety.

28-day cycles

Visits on C1D1, C1D2, C1D8, C1D15, C1D16, and Day 1 of Cycles 2-7

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• TERN-701

Trial Overview

TERN-701, a new drug aimed at treating chronic myeloid leukemia, is being tested. The study has two parts: first, finding the right dose by increasing it gradually; second, giving more people this chosen dose to see how effective and safe it is when taken daily in cycles of 28 days.

How Is the Trial Designed?

Group I: Part 2m - 500 mg Dose Experimental Treatment 1 Intervention

Dose for Part 2m was selected based on the totality of safety, PK, PD and efficacy data from Part 1 and nonclinical data. TERN-701 is administered once daily.

Group II: Part 2 - Dose 2 (500 mg) Experimental Treatment 1 Intervention

Dose 2 was selected based on the totality of safety, PK, PD and efficacy data from Part 1. TERN-701 administered once daily.

Group III: Part 2 - Dose 1 (320 mg) Experimental Treatment 1 Intervention

Dose 1 was selected based on the totality of safety, PK, PD and efficacy data from Part 1. TERN-701 administered once daily.

Group IV: Part 1- Dose Level 4 (500 mg) of TERN-701 Experimental Treatment 1 Intervention

Dose Level 4 of TERN-701 dosed once daily.

Group V: Part 1- Dose Level 3 (400 mg) of TERN-701 Experimental Treatment 1 Intervention

Dose Level 3 of TERN-701 dosed once daily.

Group VI: Part 1- Dose Level 2 (320 mg) of TERN-701 Experimental Treatment 1 Intervention

Dose Level 2 of TERN-701 dosed once daily.

Group VII: Part 1- Dose Level 1 (160 mg) of TERN-701 Experimental Treatment 1 Intervention

Dose Level 1 of TERN-701 dosed once daily.

Who Is Running the Clinical Trial?

Terns, Inc.

Lead Sponsor

Trials

5

Recruited

570+

Published Research Related to This Trial

In a study of 24 patients with acute leukemia or blast crisis of chronic myelocytic leukemia, mitoxantrone treatment led to complete remission in 5 out of 20 evaluable patients, indicating its potential efficacy in this challenging patient population.

While mitoxantrone caused moderate to severe side effects like bone marrow suppression and mucositis, it did not result in cardiotoxicity, suggesting a relatively safe profile for further investigation in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoxantrone in the treatment of relapsed and refractory acute leukemia. Meyer, P., Ho, AD., Ehninger, G., et al.[2019]

Two specific genetic variants (SNPs) rs2025501 and rs6661575 were found to increase sensitivity to cytarabine and were linked to higher treatment-related mortality (TRM) in children with acute myeloid leukemia (AML), particularly when treated with high doses of cytarabine.

The study identified another SNP, rs17202778, which significantly impacts TRM, suggesting that these genetic markers could help predict patient responses to cytarabine and guide treatment decisions in future AML trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic Variants of Cytarabine Sensitivity Associated with Treatment-Related Mortality in Pediatric AML: A Report from the Children's Oncology Group. Phillips, CL., Lane, A., Gerbing, RB., et al.[2021]

Mitoxantrone was administered to 40 patients with relapsed and refractory acute leukemia, showing promising results with complete and partial remissions, particularly in acute non-lymphocytic leukemia, where 4 complete and 6 partial remissions were observed.

The treatment was generally well-tolerated, with expected side effects like bone marrow depression and mild gastrointestinal symptoms, suggesting that mitoxantrone could be a safe and effective option for further studies in acute leukemia therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II trial of mitoxantrone in patients with relapsed and refractory acute leukemia]. Sampi, K., Ogawa, M., Kimura, I., et al.[2013]

Cytarabine is an effective treatment for hematological malignancies like acute leukemias and lymphomas, but it has a range of dose-dependent side effects, including serious conditions like bone marrow suppression and cardiomyopathy.

The abstract highlights three cases of delayed hypersensitivity reactions to cytarabine, specifically affecting the ears, which are believed to be linked to cytokine release.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytarabine ears - A side effect of cytarabine therapy. Doval, D., Kumar Sharma, S., Kumar, M., et al.[2020]

Mitoxantrone, a synthetic drug used in treating acute leukemia, showed a 48% overall response rate and a 25% complete remission rate in a five-day treatment regimen, indicating its potential effectiveness.

The drug demonstrated limited toxicity compared to traditional anthracycline antibiotics, with only mild side effects like alopecia and nausea, although the short duration of trials did not allow for assessment of cardiac toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoxantrone in relapsed and refractory acute leukemia. Prentice, HG., Robbins, G., Ma, DD., et al.[2018]

Citations

1.

ir.ternspharma.com

ir.ternspharma.com/news-releases/news-release-details/terns-announces-abstract-positive-clinical-data-tern-701

Release Details

The 24 weeks MMR achievement rate with TERN-701 is unprecedented, trending at least two times higher than the rates reported in other Phase 1 ...

2.

marketchameleon.com

marketchameleon.com/articles/b/2025/11/4/tern-701-75-percent-mmr-response-refractory-cml-phase-1-ash-spotlight

TERN-701 Shows Unprecedented 75% Response Rate in ...

TERN-701 Shows Unprecedented 75% Response Rate in Tough-to-Treat CML Patients—What Does This Mean for the Future of Leukemia Therapy? Major ...

3.

finance.yahoo.com

finance.yahoo.com/news/terns-pharmaceuticals-tern-74-1-081326271.html

Terns Pharmaceuticals (TERN) Is Up 74.1% After Positive ...

Terns Pharmaceuticals (TERN) Is Up 74.1% After Positive Phase 1 TERN-701 Data in CML Patients.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06163430

NCT06163430 | CARDINAL- A Clinical Study to Evaluate ...

CARDINAL- A Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia.

5.

onclive.com

onclive.com/view/tern-701-decreases-bcr-abl-levels-generates-molecular-responses-in-r-r-cml

TERN-701 Decreases BCR-ABL Levels, Generates ...

TERN-701 achieved a 50% cumulative MMR rate in patients without the BCR-ABL1 T315I mutation after three months of treatment. No dose-limiting ...