Safety and Anti-leukemic Activity of Vodobatinib (K0706) for Treatment of Ph+ CML Resistant/Intolerant to ≥3 Prior CML Therapies

A Two-Part Phase 1/2 Study to Determine Safety, Tolerability, Pharmacokinetics, and Activity of K0706, a Novel Tyrosine Kinase Inhibitor (TKI), in Healthy Subjects and in Subjects With Chronic Myeloid Leukemia (CML) or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Phase 1/2 study to determine safety, tolerability, pharmacokinetics, and anti-leukemic activity of Vodobatinib (K0706) in treatment-refractory/intolerant CML

Part A ( for Healthy volunteers) of the study is completed.

Part B dose-escalation study is completed. Recruitment in dose expansion is completed.

Part C study in subjects with treatment-resistant/intolerant CML is also completed.

Part A Inclusion Criteria:

• Healthy males aged 18 to 55 years

Part B Key Inclusion Criteria:

• Subjects diagnosed with Ph+ CML-CP, Ph+ CML-AP, Ph+ CML-BP, or Ph+ ALL who are refractory or intolerant to at least 3 TKIs or are not eligible (e.g.: due to comorbidities, hypersensitivity to excipients, lack of insurance coverage) for their local country's regulatory approved and medically appropriate TKIs (e.g., a TKI that is effective against mutations in the patient's tumor).

Part C Key Inclusion Criteria:

• Subjects diagnosed with Ph+ CML-CP, Ph+ CML-AP, Ph+ CML-BP, who are resistant and/or intolerant to ≥ 3 prior TKIs one of which includes ponatinib (Subjects with Ph+ ALL are not included).

Part B and C: Other Inclusion Criteria

• Willing and able to give written, and dated, informed consent
• Male or female aged ≥ 18 years
• Willing and able to comply with the scheduled visits
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Part A Exclusion Criteria:

• Any major surgery, as determined by the Investigator, within 4 weeks of IMP administration
• Inability to undergo venipuncture and/or tolerate venous access
• Positive exclusion tests: HIV, hepatitis B surface antigen, or hepatitis C virus
• Known or suspected history of significant drug abuse as judged by the Investigator

Part B and C Exclusion Criteria:

• Presence of T315I
• Any major surgery, as determined by the Investigator, within 4 weeks of IMP administration
• Inability to undergo venipuncture and/or tolerate venous access
• Positive exclusion tests: urine pregnancy tests (if applicable), HIV, hepatitis B surface antigen, or hepatitis C virus
• Known or suspected history of significant drug abuse as judged by the Investigator
• Received any other investigational agent within 30 days or a washout of at least 5 half-lives, whichever is longer of IMP administration
• Subjects who are eligible for potentially curative therapy that is available, including hematopoietic stem cell transplant
• Another primary malignancy within the past 3 years or earlier (except for adequately treated non-melanoma skin cancer or cervical cancer in situ