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

Study Overview

• Status: Terminated
• Conditions: Healthy (For Part A); Chronic Myeloid Leukemia (for Part B and C)
• Intervention / Treatment: Drug: Vodobatinib (K0706) capsules

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2; Phase 1

Expanded Access

Temporarily not available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
• France
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13273
      • Institut Paoli Calmettes
  • Rhone
    • Lyon, Rhone, France, 69373
      • Centre Leon Berard
    • Pierre-Bénite, Rhone, France, 69495
      • Centre hospitalier Lyon Sud
• Hungary
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem
• India
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Tata Memorial Hospital
    • Mumbai, Maharashtra, India, 400010
      • Prince Aly Khan Hospital
    • Pune, Maharashtra, India, 411004
      • Sahyadri Specialty Hospital
  • Tamil Nadu
    • Madurai, Tamil Nadu, India, 625107
      • Meenakshi Mission Hospital & Research Centre
  • West Bengal
    • Kolkata, West Bengal, India, 700156
      • Tata Medical Centre
• Italy
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Roma, Italy, 00161
    • Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
  • Roma, Italy, 00144
    • Ospedale Sant'Eugenio
  • Forli - Cesena
    • Meldola, Forli - Cesena, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milano
    • Monza, Milano, Italy, 20900
      • Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)
• Romania
  • Bucharest, Romania, 020125
    • Spitalul Clinic Colentina
  • Cluj-Napoca, Romania, 400124
    • Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca
  • Craiova, Romania, 200143
    • Spitalul Clinic Municipal Filantropia Craiova
• South Korea
  • Gyeonggi-do, South Korea, 11759
    • Uijeongbu Eulji Medical Center, Eulji University
  • Gyeonggi-do
    • Seoul, Gyeonggi-do, South Korea, 6591
      • The Catholic University of Korea, Seoul ST. Mary's Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • ICO Badalona - Hospital Universitari Germans Trias i Pujol
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE5 9NU
      • King's College Hospital
    • London, Greater London, United Kingdom, W120HS
      • Hammersmith Hospital
• United States
  • California
    • Downey, California, United States, 90241
      • The Oncology Institute of Hope and Innovation, Innovative Clinical Research Institute
    • Los Angeles, California, United States, 90024
      • UCLA Hematologic Malignancy Program
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Board of Regents of the University System of Georgia
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center - MAIN
  • Texas
    • Dallas, Texas, United States, 75226
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vodobatinib (K0706) capsules	Drug: Vodobatinib (K0706) capsules; Part A: Oral Vodobatinib (K0706) capsules in single ascending doses. Part B: Oral Vodobatinib (K0706) capsules in multiple ascending doses, once daily. Part C: Oral Vodobatinib (K0706) capsules at recommended phase 2 dose of 174 mg, once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Examination of the Safety and Tolerability of Single Oral Doses of K0706	Number of Participants with Adverse Events in Part A	Approximately 56 ± 2 days
To Determine the Maximum Tolerated Dose (MTD) as Determined by Frequency of Dose Limiting Toxicities	PART B	Dose Limiting toxicities observed over a 4 week period
Incidence and Severity of Treatment Emergent AEs (PART B)	Number of Participants with treatment emergent Adverse Events in Part B	All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
For CML Subjects in CP at Study Entry	PART C: Proportion of subjects achieving Major Cytogenetic Response [ defined as complete cytogenetic response (CCyR; 0% Ph+metaphases) or partial cytogenetic response (PCyR; 1-35% Ph+ metaphases)] as assessed by conventional Karyotyping of Bone marrow aspirate	All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
For CML Subjects in AP at Study Entry	PART C: Proportion of subjects achieving Major Hematologic Response [ defined as complete hematologic response (CHR) or no evidence of leukemia (NEL)] as assessed by complete blood count of peripheral blood sample	All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
For CML Subjects in BP at Study Entry	PART C: Proportion of subjects achieving Major Hematologic Response [defined as complete hematologic response (CHR) or no evidence of leukemia (NEL)] as assessed by complete blood count of peripheral blood sample	All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Characterize the Pharmacokinetics (Cmax) of K0706 After Single Oral Doses in Healthy Male Subjects	Part A	Approximately 28 ± 2 days
To Characterize the Pharmacokinetics of K0706 (Cmax) After Single Oral Doses in Fasted and Fed State in Healthy Male Subjects	Part A	Approximately 28 ± 2 days
Pharmacokinetic Profile of K0706 - Cmax [The Maximum (Peak) Observed Drug Concentration After Dose Administration]	PART B	All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706)
Pharmacokinetic Profile of Vodobatinib (K0706) - Tmax [The Time to Reach Maximum (Peak) Drug Concentration After Dose Administration]	PART B	All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706)
Pharmacokinetic Profile of Vodobatinib (K0706) - AUC[0-tau] (AUC Over the Dosing Interval of 0-24 Hours).	PART B	All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706)
In Subjects With CML- CP:Proportion of Subjects Achieving Complete Hematological Response as Assessed by Complete Blood Count of Peripheral Blood Sample	PART C	All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
In Subjects With CML- CP:Proportion of Subjects Achieving Complete Cytogenetic Response as Assessed by Conventional Karyotyping of Bone Marrow Aspirate	PART C	All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
In Subjects With CML- CP:Proportion of Subjects Achieving Major Molecular Response as Assessed by BCR-ABL Transcript Levels (BCR-ABL1 Ratio of ≤ 0.1%) in Peripheral Blood Using PCR (Polymerase Chain Reaction)	PART C	All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
In Subjects With CML-AP & BP: Proportion of Subjects Achieving Complete Cytogenetic Response as Assessed by Conventional Karyotyping of Bone Marrow Aspirate	PART C	All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
In Subjects With CML-AP & BP: Proportion of Subjects Achieving Partial Cytogenetic Response (PCyR) as Assessed by Conventional Karyotyping of Bone Marrow Aspirate	Part C	All subjects will be followed up for 60 months from the first dose of K0706
In Subjects With CML-AP & BP: Proportion of Subjects Achieving Major Molecular Response as Assessed by BCR-ABL Transcript Levels (BCR-ABL1 Ratio of ≤ 0.1%) in Peripheral Blood Using PCR (Polymerase Chain Reaction)	PART C	All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
Time to Major Cytogenetic Response (MCyR): Time to MCyR is the Time From First Dose to First MCyR (0-35% Ph+ Metaphases); Computed Only for CML-CP Subjects Who Achieved MCyR	PART C; Time to response was calculated as time from date of first dose to date of first occurrence of best response	All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
Time to Major Molecular Response : Time to MMR is the Time From First Dose to First MMR (BCR-ABL1 Ratio of ≤ 0.1%) Computed Only for CML-CP Subjects Who Achieved MMR	PART C; Time to response was calculated as time from date of first dose to date of first occurrence of best response	All subjects will be followed up for 60 months from the first dose of Vodobatinib (K0706)
In All Subjects Progression Free Survival (PFS)	PART C	All subjects will be followed up at 12, 24, 36 months from the first dose of K0706 and beyond, until intolerance, disease progression or subject withdrawal from the study.
In All Subjects Overall Survival (OS)	PART C	All subjects will be followed up at 12, 24, 36 months from the first dose of K0706 and beyond, until intolerance, disease progression or subject withdrawal from the study.
Incidence and Severity of Treatment Emergent AEs (PART C)	Number of Participants with treatment emergent Adverse Events in Part C	All subjects will be followed up for up to 60 months from the first dose of Vodobatinib (K0706), unless subject discontinues due to intolerance or progression of disease.
Pharmacokinetic Profile of K0706 - Cmax [The Maximum (Peak) Observed Drug Concentration After Dose Administration]	PART C	All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706)
Pharmacokinetic Profile of Vodobatinib (K0706) - Tmax [The Time to Reach Maximum (Peak) Drug Concentration After Dose Administration]	PART C	All subjects will be followed for up to approximately 60 months after the first dose of Vodobatinib (K0706)
To Characterize the Pharmacokinetics (AUC(0-inf)) of K0706 After Single Oral Doses in Healthy Male Subjects	Part A	Approximately 28 ± 2 days
To Characterize the Pharmacokinetics of K0706 (AUC(0-inf)) After Single Oral Doses in Fasted and Fed State in Healthy Male Subjects	Part A	Approximately 28 ± 2 days

Collaborators and Investigators

• Sponsor: Sun Pharma Advanced Research Company Limited

Publications and helpful links

General Publications

• Cortes JE, Kim DW, Saikia T, Khattry N, Rathnam K, Alvarado Y, Hannah G, Tantravahi SK, Apperley JF, Charbonnier A, Garcia-Gutierrez V, Lucchesi A, Dima D, Illes A, Popov VM, Abruzzese E, Nag A, Apte S, Badar T, Yao SL, Saxena U, Sreenivasan J, Inamdar S, Chimote G, Nicolini FE. Vodobatinib for patients with Philadelphia chromosome-positive chronic myeloid leukaemia resistant or intolerant to multiple lines of previous therapy: an open-label, multicentre, phase 1/2 trial. Lancet Haematol. 2025 Mar;12(3):e201-e213. doi: 10.1016/S2352-3026(24)00354-5. Epub 2025 Feb 7.

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2016
• Primary Completion (Actual): January 3, 2025
• Study Completion (Actual): January 3, 2025

Study Registration Dates

• First Submitted: December 10, 2015
• First Submitted That Met QC Criteria: December 10, 2015
• First Posted (Estimated): December 14, 2015

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: CML; Chronic Myelogenous Leukemia; K0706; Vodobatinib; ponatinib-refractory/intolerant; treatment refractory chronic myeloid leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Myeloproliferative Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Pharmaceutical Preparations; Dosage Forms; Capsules
• Other Study ID Numbers: CLR_15_03 V 12 Amendment 12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No