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

Completed · Phase 1/Phase 2

Conditions studied: Chronic Lymphocytic Leukemia, Waldenstrom Macroglobulinemia, Mantle Cell Lymphoma, Marginal Zone Lymphoma, B-cell Lymphoma, Small Lymphocytic Lymphoma

In brief

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

Key facts

Study ID

NCT03740529

Run by

Loxo Oncology, Inc.

People needed

803

Starts

2019-03-15

Expected to finish

2025-12-23

Last updated by the study team

2026-01-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 inhibitor-containing regimen when a BTK inhibitor is approved as first line therapy (Phase 1) OR with prior treatment defined by phase 2 cohort (Phase 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; no prior venetoclax is permitted (Phase 1b Arm A Patients only).
• Histologically confirmed relapsed/refractory CLL in whom venetoclax + rituximab is appropriate standard salvage treatment; no prior venetoclax is permitted (Phase 1b Arm B 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 (defined as following menarche and not postmenopausal [and 2 years of non-therapy-induced amenorrhea] or surgically sterile) to observe conventional and effective birth control.

You may not qualify if…

• Investigational agent or anticancer therapy within 5 half-lives or 14 days, whichever is shorter, prior to planned start of specified study therapy except antineoplastic and immunosuppressant monoclonal antibody treatment must be discontinued a minimum of 4 weeks prior to the first dose of pirtobrutinib. In addition, no concurrent systemic anticancer therapy is permitted.
• Major surgery within 4 weeks prior to planned start of specified study therapy.
• 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) prior to planned start of specified study therapy.
• Known central nervous system (CNS) involvement by systemic lymphoma. Patients with previous treatment for CNS involvement who are neurologically stable and without evidence of disease may be eligible and enrolled to phase 2 Cohort 7 if a compelling clinical rationale is provided by the Investigator and with documented Sponsor approval.
• 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 pirtobrutinib.
• Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.
• Patients who have tested positive for human immunodeficiency virus (HIV) are excluded. For patients with unknown HIV status, HIV testing will be performed at Screening and result should be negative for enrollment.
• Clinically significant active malabsorption syndrome.
• Current treatment with certain strong CYP3A4 inhibitors or inducers and/or strong P-gp inhibitors.
• For patients enrolled to phase 1b Arm A or B: Patients with prior treatment with venetoclax or other BCL-2 inhibitors.
• Prior treatment with pirtobrutinib.
• Active second malignancy unless in remission and with life expectancy > 2 years.
• Known hypersensitivity to any component or excipient of pirtobrutinib.
• For patients enrolled to phase 1b Arm B: Patients with prior significant hypersensitivity, allergy, or anaphylactic reaction to rituximab/biosimilar requiring discontinuation.
• Patients with prior significant hypersensitivity to rituximab requiring discontinuation, prior allergic or anaphylactic reaction to rituximab (Phase 1b Arm B Patients only).

Where it is running

• Scripps Coastal Medical Center — San Diego, California, United States
• University of California San Francisco, Medical Center at Paranassus — San Francisco, California, United States
• Smilow Cancer Hospital at Yale-New Haven — New Haven, Connecticut, United States
• Mayo Clinic-Jacksonville — Jacksonville, Florida, United States
• Florida Cancer Specialists ORLANDO/DDU — Lake Mary, Florida, United States
• Sylvester Comprehensive Cancer Center — Miami, Florida, United States
• Florida Cancer Specialists — Sarasota, Florida, United States
• Emory Clinic — Atlanta, Georgia, United States
• Northwestern University — Chicago, Illinois, United States
• University of Kansas Medical Center — Kansas City, Kansas, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Mayo Clinic — Rochester, Minnesota, United States
• University of Nebraska Medical Center — Omaha, Nebraska, United States
• Roswell Park Cancer Institute — Buffalo, New York, United States
• Northwell Health — New Hyde Park, New York, United States
• Columbia University Medical Center — New York, New York, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• University of North Carolina at Chapel Hill — Chapel Hill, North Carolina, United States
• Durham VA Medical Center — Durham, North Carolina, United States
• Duke University Medical Center — Durham, North Carolina, United States
• Cleveland Clinic Foundation — Cleveland, Ohio, United States
• Ohio State University Hospital — Columbus, Ohio, United States
• University of Pennsylvania Hospital — Philadelphia, Pennsylvania, United States
• Sarah Cannon Research Institute SCRI — Nashville, Tennessee, United States
• Mayo Clinic of Scottsdale — Scottsdale, Arizona, United States

Full record on ClinicalTrials.gov

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