ENSAYO CLÍNICO

Reclutando

Fase I-II

Leucemia mieloide crónica, Linfoma, Leucemia

Abril, 2024

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1. Male or female participants 18 years of age at the time of signing the informed consent or the legal age of adulthood in countries where the local law considers the legal adult age tobe > 18 years of age
2. Have an ECOG performance status score of 0 to 1
3. Have an established cytopathologically confirmed diagnosis of BCR::ABL1 positive CML in CP, and meet at least 1 of the following: For Part 1: Participants without the BCR::ABL1 T315Im who: o Received 2 or more tyrosine kinase inhibitors (TKIs) and have experienced treatment failure, suboptimal response, or treatment intolerance as determined by the investigator OR o Experienced treatment failure or suboptimal response (as determined by the investigator) to frontline therapy with dasatinib, nilotinib, or bosutinib and are ineligible for alternative TKIs per the investigators discretion Participants with BCR::ABL1 T315Im who received 1 or more TKIs and have experienced treatment failure, suboptimal response, or intolerance, as determined by the investigator.; pParticipants should have received prior treatment with ponatinib unless the participant is ineligible for or is not a candidate to receive ponatinib, in the opinion of the investigator For Part 2 (randomized dose expansion): Participants who have experienced treatment failure or suboptimal response (as determined by the investigator) to at least 1 but not more than 4 TKIs. Change of TKI due to intolerance without associated treatment failure or suboptimal response will not be counted towards the upper limit of 4 TKIs.
4.Adequate organ function, as assessed by the following screening laboratory values obtained locally: ANC 1500/mm3 Hemoglobin 8.0 g/dL Platelets 100,000/mm3 CrCl 50 mL/min Serum total bilirubin 1.5 × ULN ( for participants with Gilberts syndrome, serum total bilirubin 3 × ULN) AST (SGOT) and ALT (SGPT) 2.5 × ULN For Part 2m (mutation cohort): Participants with BCR::ABL1 resistance mutation(s) including T315I, M244V, H396R, E355G, F359I/C/V, and I502L. Other mutations not listed, but present in the P-loop, active site, A-loop, and C-helix, may be considered for inclusion on a case-by-case basis. AND Have received 1 or more TKIs and have experienced treatment failure, suboptimal response, or intolerance, as determined by the investigator. Participants should have received prior treatment with ponatinib unless the participant is ineligible for or is not a candidate to receive ponatinib, in the opinion of the investigator

1. Peripheral blasts 10%, peripheral basophils 20% and/or additional new clonal chromosomal abnormalities in Ph+ cells
10. Have a history of acute pancreatitis within 1 year of trial entry or chronic pancreatitis
11. Have acute or chronic liver disease (including hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B hepatic cirrhosis)
12. Have known significant mental illness or other condition such as active alcohol or other substance abuse or addiction, or other psychosocial conditions, that, in the opinion of the investigator, predisposes the participant to high risk of noncompliance with the protocol; where required by local law, participants will be excluded who are under court protection, persons not affiliated with the local social security system and protected adults
13. Have any of the following cardiovascular conditions: Uncontrolled severe hypertension despite current therapy (blood pressure 150/90 mmHg on more than 1 occasion at least 24 hours apart) within the 28 days prior to the first dose of TERN-701 Symptomatic congestive heart failure, defined as Class II of the New York Heart Association functional classification Recent myocardial infarction (within 3 months) Clinically significant arrhythmias that would preclude participation, in the judgment of the investigator Known history of marked prolongation of QT/QTc interval that, in the judgment of the investigator, would preclude participation QTc interval> 470 ms for women and > 450 ms for men using Fridericias QT correction formula
14. Female participants who are pregnant or lactating
2. CML with atypical transcript (e13a3,e14a3, e8a2, e1a2 and/or e6a2)
3. Mutation Status Exclusions:For Part 1: The following known BCR:ABL1 myristoyl domain resistance mutations: A337V, P465S, V468F, I502L, G463D, G463S, C464W and mutation(s) in the SH2/SH3 contact sites or C lobe For Part 2 randomized dose expansion. The following known mutations in the BCR::ABL1 domain: T315I, M244V, E355D/G/A, A337V, A344V, M351T, P465S, V468F, I502L, G463D, G463S,F359C/V/I, F486S, C464W, mutation(s) in the C-terminal lobe, as well as those in the SH2 and/or SH3 contact sites along with any mutations in the DFG motif (D381, F382, G383) of the activation loop, which extends from the C-lobe
4. Systemic antineoplastic therapy (including prior TKIs, interferon-alfa, therapeutic antibodies, chemotherapy) or other experimental therapy within 7 days or 5 half-lives (whichever is longer) before the first dose of TERN-701; hydroxyurea, if used for leukocytosis, should be weaned off before the first dose of TERN-701
5. Unable to swallow oral medication
6. Have had major surgery within 4 weeks before the start of trial intervention
7. History of significant small bowel resection, gastric bypass, use of feeding tubes or other condition that may preclude adequate absorption of orally dosed trial intervention
8. Have completed previous anticancer therapy without resolution of all associated clinically significant toxicity (to Grade 2 or baseline) prior to TERN-701 administration
9. Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessments per the investigators discretion

1. Part 1 To evaluate the safety and tolerability of TERN-701 in participants with previously treated CP-CML 2. Part 2 To evaluate the efficacy of TERN-701 in participants with previously treated CP-CML

chronic leukemia, chronic myeloid leukemia, leucemia, leucemia cronica, leukemia