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A Study of Oral LOXO-305 in Patients With Previously Treated CLL / SLL or NHL

Trial Status: Active

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.

Inclusion Criteria

  • Histologically confirmed CLL/SLL, WM, or NHL intolerant to either ≥ 2 prior standard of care regimens given in combination or sequentially OR have received 1 prior BTK-containing regimen when a BTK inhibitor is approved as first line therapy (Phase 1 and 2 Patients only).
  • Adequate hematologic function (Phase 1 and 1b Patients only)
  • Responsive to transfusion support if given for thrombocytopenia or anemia (Phase 1 and 1b Patients only)
  • Histologically confirmed relapsed/recurrent CLL in whom venetoclax is appropriate standard salvage treatment (Phase 1b Arm A Patients only)
  • Histologically confirmed relapsed/refractory CLL in whom venetoclax + rituximab is appropriate standard salvage treatment (Phase 1b Arm B Patients only)
  • Histologically confirmed CD20(+) non-GCB DLBCL, FL, or MCL who have received ≤1 prior regimen of treatment, with ≥ 1 site of measurable disease, and for which appropriate treatment is the combination of rituximab with standard CHOP (R-CHOP) chemotherapy (Phase 1b Arm C Patients only)
  • Eastern Cooperative Oncology Group (ECOG) 0-2.
  • Adequate 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.

Exclusion Criteria

  • Investigational agent or anticancer therapy within 5 half-lives prior to planned start of LOXO-305 except therapeutic monoclonal antibody treatment must be discontinued a minimum of 4 weeks prior to the first dose 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 with warfarin.
  • 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 60 days (180 days before the PK trigger).
  • Known central nervous system (CNS) involvement by lymphoma.
  • Active uncontrolled auto-immune cytopenia where new therapy introduced or concomitant therapy escalated within the 4 weeks prior to study enrollment is required to maintain adequate blood counts..
  • 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.
  • Known hypersensitivity to any component or excipient of LOXO-305
  • Patients with prior significant hypersensitivity to rituximab requiring discontinuation, prior allergic or anaphylactic reaction to rituximab (Phase 1b Arm B and Arm C Patients only)

California

San Francisco
UCSF Medical Center-Mount Zion
Status: ACTIVE
Contact: UCSF Clinical Trials
Phone: 877-827-3222

Florida

Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: ACTIVE

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: APPROVED

Kansas

Kansas City
University of Kansas Cancer Center
Status: IN_REVIEW

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: ACTIVE
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE

New York

Buffalo
Roswell Park Cancer Institute
Status: ACTIVE
New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: ACTIVE

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: IN_REVIEW
Columbus
Ohio State University Comprehensive Cancer Center
Status: ACTIVE

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: ACTIVE

South Carolina

Charleston
Medical University of South Carolina
Status: IN_REVIEW

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: IN_REVIEW

This study includes 3 parts: phase 1 (LOXO-305 monotherapy dose escalation and dose expansion), phase 1b (LOXO-305 combination therapy dose expansion), and phase 2 (LOXO-305 monotherapy 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 in phase 1 dose escalation, enrollment will continue to phase 1 dose expansion and can commence to phase 1b (Arms A and C). Subsequent enrollment to phase 1b (Arm B) and phase 2 will follow when appropriate. For phase 2, 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.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Loxo Oncology, Inc.

  • Primary ID LOXO-BTK-18001
  • Secondary IDs NCI-2019-02015
  • Clinicaltrials.gov ID NCT03740529