Clinical Trials

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).