A Study of Oral LOXO-305 in Patients With Previously Treated CLL / SLL or NHL
- 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.
- 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)
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
Loxo Oncology, Inc.
- Primary ID LOXO-BTK-18001
- Secondary IDs NCI-2019-02015
- Clinicaltrials.gov ID NCT03740529