Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion
Bita Fakhri

Description

Summary

This is an open-label, multi-center Phase 1/2 study of oral LOXO-305 in patients with CLL/SLL and NHL who have failed or are intolerant to standard of care.

Official Title

A Phase 1/2 Study of Oral LOXO-305 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Non-Hodgkin Lymphoma (NHL)

Details

This study includes 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). In phase 1, patients will be enrolled using an accelerated titration design. The starting dose of LOXO-305 in oral tablet form is 25 mg/day (e.g., 25 mg once daily [QD]). Once the MTD and/or RP2D is identified, patients will be enrolled to one of six phase 2 dose expansion cohorts depending on tumor histology, tumor genotype, and prior treatment history. Cycle length will be 28 days.

Keywords

Chronic Lymphocytic Leukemia Waldenstrom Macroglobulinemia Mantle Cell Lymphoma Marginal Zone Lymphoma B-cell Lymphoma Small Lymphocytic Lymphoma Loxo LOXO-305 BTK Bruton's tyrosine kinase CLL SLL NHL C481S C481 Ibrutinib Acalabrutinib Zanubrutinib BGB-3111 GS-4059 ONO-4059 Tirabrutinib Non-Hodgkin Lymphoma BTK Intolerant C481S Mutation DLBCL (Diffuse Large B-cell lymphoma) Follicular Lymphoma Lymphoma Leukemia Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, B-Cell Lymphoma, Mantle-Cell Lymphoma, B-Cell, Marginal Zone CLL/SLL/WM/MCL/MZL/other NHL intolerant to prior BTKi Other

Eligibility

You can join if…

Open to people ages 18 years and up

  • Histologically confirmed CLL/SLL or NHL intolerant to standard of care therapies.
  • Histologically confirmed CLL/SLL or NHL which has failed standard of care therapies
  • ≥ 2 prior lines of therapy.
  • For initial phase 1 patients, able to tolerate potentially subtherapeutic doses of LOXO-305 for the 28-day DLT window in the opinion of the investigator and with documented sponsor approval.
  • Eastern Cooperative Oncology Group (ECOG) 0-2.
  • Adequate hematologic, hepatic and renal function.
  • Ability to receive study drug therapy orally.
  • Willingness of men and women of reproductive potential to observe conventional and effective birth control.

You CAN'T join if...

  • Transformation (e.g., Richter's transformation, prolymphocytic leukemia, transformed NHL, blastoid lymphoma) prior to planned start of LOXO-305.
  • Investigational agent or anticancer therapy within 2 weeks prior to planned start of LOXO-305. In addition, no concurrent investigational therapy is permitted.
  • Major surgery within 4 weeks prior to planned start of LOXO-305.
  • Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of study treatment.
  • Pregnancy or lactation.
  • Patients requiring therapeutic anticoagulation.
  • Any unresolved toxicities from prior therapy greater than CTCAE (version 5.0) Grade 2 or greater at the time of starting study treatment except for alopecia.
  • History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T-cell (CAR-T) therapy within the past 100 days (180 days before the PK trigger).
  • Known central nervous system (CNS) involvement by lymphoma.
  • Active uncontrolled auto-immune cytopenia.
  • Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-305.
  • Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.
  • Tested positive for Human Immunodeficiency Virus (HIV) is excluded.
  • Clinically significant active malabsorption syndrome.
  • Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors
  • Treatment with proton pump inhibitors (PPIs) within 7 days of starting LOXO-305.

Active second malignancy unless in remission and with life expectancy > 2 years.

Locations

  • University of California, San Francisco accepting new patients
    San Francisco California 94143 United States
  • Swedish Cancer Institute accepting new patients
    Seattle Washington 98104 United States

Lead Scientist

  • Bita Fakhri
    Assistant Professor, Medicine. Authored (or co-authored) 11 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Loxo Oncology, Inc.
ID
NCT03740529
Phase
Phase 1/2
Study Type
Interventional
Last Updated