Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Ponatinib
ponatinib- Phase 1 · 1 trial · 2 indications
DLT was evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 and was defined as any of the following events: 1. Grade greater than or equal to (\>=) 3 non-hematologic, with the exception of medically controllable toxicities (example; nausea, vomiting, fatigue, electrolyte disturbances, hypersensitivity reactions) lasting \<=3 days, but excluding alopecia; 2. Missed doses: \>25% of planned ponatinib doses over 28 days due to AEs in the first cycle; 3. Febrile neutropenia (the occurrence of an ANC \<500/microliter concurrently with a temperature elevation of \>101 degree Fahrenheit), when neutropenia is not related to underlying acute leukemia, as defined hematologic toxicity: Dose-limiting hematologic toxicity is the occurrence of a Grade 4 cytopenia \>28 days, not related to underlying disease according to the investigator. Bone marrow examination must demonstrate \<5% cellularity.
MCyR was defined as percentage of participants who achieved a complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR) after the initiation of study treatment. Cytogenic response was the percentage of Philadelphia chromosome positive (Ph+) metaphases in bone marrow. CCyR: no Ph+ cells. PCyR: 1% to 35% Ph+ cells. Participants entering the study already in PCyR had to achieve a CCyR in order to be considered a success for the confirmed MCyR rate.
MaHR was defined as percentage of participants with complete hematologic response (CHR) or no evidence of leukemia (NEL). MaHR response was confirmed by a peripheral blood complete blood count (CBC) and differential no earlier than 28 days after the response was observed. Response criteria for CHR was reported as white blood cells (WBC)\<=institutional upper limit of normal (ULN), absolute neutrophil count (ANC)\>=1000/mm\^3, platelets\>=100,000/mm\^3, no blasts or promyelocytes in peripheral blood, BM blasts \<=5%, \<5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood \<5%, no extramedullary involvement; Response criteria for NEL reported as WBC\<=institutional ULN, no blasts or promyelocytes in peripheral blood, BM blasts \<=5%, \<5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood \<5%, no extramedullary involvement, at least 1 of the following: (i) 20,000/mm\^3\<=platelets\<100,000/mm\^3; (ii) 500/mm\^3\<=ANC\<1000/mm\^3.
| Arm | Type | Description |
|---|---|---|
| Phase 1 dose escalation | EXPERIMENTAL | Phase 1 |
| Phase 2 expansion | EXPERIMENTAL | Phase 2 |
| Name | Type | Description |
|---|---|---|
| ponatinib - Phase 1 | DRUG | 30 mg dose of ponatinib taken orally once daily for at least the first 6 patients. If no dose-limiting toxicities are observed, the next patients will receive 45 mg dose of ponatinib taken orally once daily. Once the recommended dose is confirmed, all patients may receive the recommended dose, at the investigators' discretion. |
| ponatinib - Phase 2 | DRUG | Recommended dose of ponatinib as determined in the dose escalation phase. In addition, 3 patients will receive 15 mg dose once daily for 8 days for PK testing. These PK patients may be allowed to receive the recommended dose after PK testing is complete, at the investigators' discretion. |
Inclusion Criteria: 1. Patients must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL, as follows: * All patients must have screening bone marrow (BM) cytogenetics with conventional banding performed within 42 days prior to beginning treatment. * Examination of at least 20 m...
Ponatinib is an investigational small molecule being studied for B Acute Lymphoblastic Leukemia with t(9;22)(q34.1;q11.2), Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL), and Chronic Myeloid Leukemia (CML), including chronic phase CML. It is in Phase 2 clinical development for these oncology indications.
Ponatinib is a kinase inhibitor, belonging to the -tinib class of drugs. It targets BCR-ABL1, the fusion protein characteristic of Philadelphia Chromosome Positive leukemias. Its development is biomarker-selected, focusing on patients with the t(9;22) translocation that produces the BCR-ABL1 fusion.
Ponatinib is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. The drug is currently in Phase 2 clinical trials for chronic myeloid leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia.
Ponatinib is in Phase 2 clinical development. It is an investigational drug, not yet approved by regulatory authorities. Clinical trials have been conducted in multiple countries, including the United States, Japan, and various European and Asian nations.
Ponatinib has been studied in several clinical trials. NCT01207440 is a Phase 2 trial in chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia with 449 participants. NCT02467270 is a Phase 2 trial in resistant chronic phase CML with 283 participants. NCT00660920 and NCT01667133 are completed Phase 1 trials.
Yes, Ponatinib was formerly known as AP24534. The Phase 1 trial NCT00660920 was titled 'Safety Study of AP24534 to Treat Chronic Myelogenous Leukemia (CML) and Other Hematological Malignancies,' confirming that AP24534 is an earlier name for the same drug.