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

Part of paid clinical trials in Phoenix, Arizona.

Sponsor
Sumitomo Pharma America, Inc.
Study ID
NCT03572634
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • TP-0903 — DRUG
    Monotherapy: PHASE 1: TP-0903 will be a 25 mg flat dose. The study drug will be administered orally once daily for 28 days (each cycle is 28 days; no drug-free period). Patients may continue to receive TP-0903 in 28-day cycles at the same dose given during Cycle 1 until they experience unacceptable toxicity or unequivocal disease progression. No intrapatient escalation of the TP-0903 dose is permitted. PHASE 2: The starting dose of TP-0903 will be the RP2D determined during Phase 1. TP 0903 will be administered orally at a fixed dose once daily for 28 days (each cycle is 28 days; no drug-free period) with repeated cycles permitted until a patient experiences unacceptable toxicity or unequivocal disease progression.
  • TP-0903 and ibrutinib combination therapy — COMBINATION_PRODUCT
    Combination therapy: PHASE 1: TP-0903 and ibrutinib combination therapy: The starting dose of TP-0903 will be a 20 mg flat dose. TP-0903 will be administered orally once daily for 28 days (each cycle is 28 days; no drug-free period). Patients will also receive ibrutinib at the same dose that they were receiving immediately prior to study enrollment. Patients should continue with the combination of ibrutinib and TP-0903 for at least 3 months after study start. PHASE 2: The starting dose of TP-0903 will be the RP2D determined during Phase 1. Patients will also receive ibrutinib at the same dose that they were receiving immediately prior to study enrollment. Both TP 0903 and ibrutinib will be administered orally at fixed doses once daily for 28 days (each cycle is 28 days; no drug-free period).

Study Details

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.

Key Dates

Start date
Jun 10, 2019
Status verified
Nov 2023
Primary completion
Jan 21, 2020
Completion
Jan 21, 2020

Study Design

Enrollment
3 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Group 1-TP 0903 monotherapy
    Adult patients with CLL/SLL who: are intolerant to, or have had progressive disease on B-cell receptor antagonists, BCL-2 antagonists or other investigational treatments for CLL/SLL
  • Experimental: Group 2-TP-0903 and ibrutinib combination therapy
    Adult patients with CLL/SLL who: have progression of disease on ibrutinib, yet the treating provider considers continuation of ibrutinib therapy to be in the best interest of the patient

Primary Outcome Measure

PHASE 1: Incidence of Dose-limiting Toxicities (DLTs) and Treatment Emergent Adverse Events. [ Time Frame: 28 days ]

Locations (6)

FacilityCityStateZIPSite coordinators
Mayo Clinic ArizonaPhoenixArizona85054-
Mayo Clinic FloridaJacksonvilleFlorida32224-
Mayo Clinic RochesterRochesterMinnesota55905-
Washington University - St LouisSt LouisMissouri63130-
Cornell UniversityNew YorkNew York10065-
Duke UniversityDurhamNorth Carolina27705-

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Mayo Clinic Arizona· Phoenix, AZMayo Clinic Florida· Jacksonville, FLMayo Clinic Rochester· Rochester, MNWashington University - St Louis· St Louis, MOCornell University· New York, NYDuke University· Durham, NC

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