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NCT03572634

Phase 1/2 Study of TP-0903 (an Inhibitor of AXL Kinase) in Patients With Previously Treated CLL

Terminated Phase 1, PHASE2 Results posted Last updated 9 November 2023
What this trial tests

Phase 1, PHASE2 trial testing TP-0903 in Chronic Lymphocytic Leukemia in 3 participants. Terminated before completion.

Timeline
10 June 2019
Primary endpoint
21 January 2020
21 January 2020

Quick facts

Lead sponsorSumitomo Pharma America, Inc.
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment3
Start date10 June 2019
Primary completion21 January 2020
Estimated completion21 January 2020
Sites6 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Sumitomo Pharma America, Inc. — full company profile →

Who can join

18 and older, any sex, with Chronic Lymphocytic Leukemia or CLL. Patients with the condition only — healthy volunteers not accepted.

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events (TEAEs) were defined as all AEs that begin on or after the date of first dose of study drug. All patients in the study participated in Phase 1; a 30 day follow-up visit as part of the protocol noted patients undergo a safety evaluation in which the patient's condition during the 30 days after the last dose of study drug can be assessed. There is a visit window of up to 14 days after completion of 30 days from the last dose (ie, within 45 days after last dose).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TP-0903 Monotherapy (25mg Dose of TP-0903)
Serious: 0/1 (0%)
Deaths: 0/1
TP-0903 and Ibrutinib Combination Therapy (20 mg Dose of TP-0903)
Serious: 2/2 (100%)
Deaths: 0/2

Serious adverse events (4 terms)

ReactionSystemTP-0903 Monotherapy (25mg …TP-0903 and Ibrutinib Comb…
Lung InfectionInfections and infestations
Increased Alanine Aminotransferase and Aspartate Aminotransferase levelsInvestigations
PyrexiaGeneral disorders
EncephalopathyNervous system disorders
Other adverse events (46 terms — click to expand)

ReactionSystemTP-0903 Monotherapy (25mg …TP-0903 and Ibrutinib Comb…
Lung InfectionInfections and infestations
HivesSkin and subcutaneous tissue disorders
Geographic tongue with aphthous ulcersGastrointestinal disorders
NauseaGastrointestinal disorders
PyrexiaGeneral disorders
Decreased bilirubin levelInvestigations
ThrombocytopeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
DiarrheaGastrointestinal disorders
Increased alkaline phosphatase levelInvestigations
Laryngeal hemorrhageRespiratory, thoracic and mediastinal disorders
Weight gainInvestigations
Arthropod biteInjury, poisoning and procedural complications
CoughRespiratory, thoracic and mediastinal disorders
Lymphocyte Count IncreaseInvestigations
Nail InfectionsInfections and infestations
Fungal infectionInfections and infestations
PurpuraSkin and subcutaneous tissue disorders
ChillsGeneral disorders
HeadacheNervous system disorders
HypoalbuminemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
Increased Alanine AminotransferaseInvestigations
Increased Aspartate AminotransferaseInvestigations
DsypneaRespiratory, thoracic and mediastinal disorders
HyperglycemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
LeukocytosisBlood and lymphatic system disorders
MalaiseGeneral disorders
Urinanry IncontienceRenal and urinary disorders
HyperhidrosisSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
HypoglycemiaMetabolism and nutrition disorders
Nasal CongestionRespiratory, thoracic and mediastinal disorders
AnorexiaMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
Weight lossInvestigations
LeukopeniaBlood and lymphatic system disorders
Edema LimbsGeneral disorders
DeliriumPsychiatric disorders

Most-reported serious reactions: Lung Infection, Increased Alanine Aminotransferase and Aspartate Aminotransferase levels, Pyrexia, Encephalopathy.

Data from ClinicalTrials.gov NCT03572634 adverse events section.

Sponsor's own description

TP-0903 is an inhibitor of AXL kinase. TP-0903 has shown potent inhibition of AXL kinase and other TAM family members in a biochemical kinase assay. TP-0903 demonstrates corresponding activity in cancer cell lines and mouse xenograft efficacy models. TP-0903 is shown to block cancer cell epithelial-to-mesenchymal transitions. AXL was identified as a potential therapeutic target in chronic lymphocytic leukemia (CLL). TP 0903 was shown to induce apoptosis in CLL B-cells taken directly from patients.TP-0903 was equally potent against CLL cells regardless of risk-factor. TP-0903 is a novel oral inhibitor that targets AXL kinase and reverses the mesenchymal phenotype associated with advanced cancers. TP-0903 has demonstrated profound single agent activity in CLL B cells taken directly from patients even if the patient has high risk factors (ie, 17p/P53 deletions) or progressed on other agents (ie, ibrutinib). TP-0903 is currently being evaluated in patients with refractory solid tumors (TP-0903-101). This proposed study is designed to identify the maximum tolerated dose (MTD), safety profile and recommended Phase 2 dose (RP2D) of TP-0903 in patients with previously treated CLL. Treatment cycles may be repeated if the patient continues to show benefit and if TP-0903 is reasonably well tolerated. The study will investigate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of TP-0903.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. EMT, MET, Plasticity, and Tumor Metastasis.
    Bakir B, Chiarella AM, Pitarresi JR, Rustgi AK. · · 2020 · cited 770× · PMID 32800658 · DOI 10.1016/j.tcb.2020.07.003
  2. AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications.
    Zhu C, Wei Y, Wei X. · · 2019 · cited 398× · PMID 31684958 · DOI 10.1186/s12943-019-1090-3
  3. Targeting Tyro3, Axl and MerTK (TAM receptors): implications for macrophages in the tumor microenvironment.
    Myers KV, Amend SR, Pienta KJ. · · 2019 · cited 333× · PMID 31088471 · DOI 10.1186/s12943-019-1022-2
  4. Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy.
    Carter JL, Hege K, Yang J, Kalpage HA, et al · · 2020 · cited 148× · PMID 33335095 · DOI 10.1038/s41392-020-00361-x
  5. Lifting the innate immune barriers to antitumor immunity.
    Rothlin CV, Ghosh S. · · 2020 · cited 63× · PMID 32273348 · DOI 10.1136/jitc-2020-000695
  6. Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer.
    Tanaka M, Siemann DW. · · 2021 · cited 60× · PMID 34576116 · DOI 10.3390/ijms22189953
  7. The Role of the Receptor Tyrosine Kinase Axl in Carcinogenesis and Development of Therapeutic Resistance: An Overview of Molecular Mechanisms and Future Applications.
    Wium M, Ajayi-Smith AF, Paccez JD, Zerbini LF. · · 2021 · cited 56× · PMID 33806258 · DOI 10.3390/cancers13071521
  8. AXL as a Target in Breast Cancer Therapy.
    Colavito SA. · · 2020 · cited 50× · PMID 32148495 · DOI 10.1155/2020/5291952

Verify or expand the search:

Other trials of TP-0903

Trials testing the same drug.

Other recruiting trials for Chronic Lymphocytic Leukemia

Currently open trials in the same condition.

Other Sumitomo Pharma America, Inc. trials

Trials by the same sponsor.

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