Study of Oral LOXO-338 in Patients With Advanced Blood Cancers

• Status: Recruiting
• Trial end date: 2024-04-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to find out whether the study drug, LOXO-338, is safe and effective in patients with advanced blood cancer. Patients must have already received standard therapy. The study may last up to approximately 3 years.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eli Lilly and Company
• Collaborator: Loxo Oncology, Inc.

Criteria

Inclusion Criteria:

• B-cell malignancy.

• Patients must have received prior therapy.

• Patients must have an objective indication for therapy.

• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2.

• Anticipated life expectancy of greater than or equal to (≥) 12 weeks.

• Adequate bone marrow function.

• Adequate hepatic function.

• Creatinine clearance of ≥ 60 milliliters (mL)/minute.

• Ability to swallow tablets.

• Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.

• Prior treatment-related adverse events (AEs) must have recovered to grade less than or equal to (≤) 1 or pretreatment baseline, with the exception of alopecia.

• Men with partners of childbearing potential or women of childbearing potential (WOCBP) must agree to use highly effective birth control.

• WOCBP must not be pregnant.

Exclusion Criteria:

• Prior to identification of the RP2D (Dose Expansion) of LOXO-338, a history of known, active or suspected:

• Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocyticleukemia, or Hodgkin lymphoma

• Transformed low grade lymphoma

• Burkitt or Burkitt-like lymphoma

• Multiple myeloma

• Lymphoblastic lymphoma or leukemia

• Posttransplant lymphoproliferative disorder

• Known or suspected history of central nervous system (CNS) involvement.

• History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T cell (CAR-T) therapy within the past 60 days and with any of the following:

• Active graft versus host disease (GVHD)

• Cytopenias from incomplete blood cell count recovery post-transplant or CAR-T therapy

• Need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity Grade > 1 from CAR-T therapy

• Ongoing immunosuppressive therapy

• Known human immunodeficiency virus (HIV) positive, regardless of cluster of differentiation 4 (CD4) count. Unknown or negative status eligible.

• Inability to take necessary uric acid lowering agents (i.e., allopurinol, rasburicase, orfebuxostat).

• Concurrent anticancer therapy.

• Concurrent treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers that can include antifungals.

• Use of ≥ 20 milligrams (mg) prednisone once a day (QD) or equivalent dose of steroid per day, within 7 days of start of study treatment. Patients may not be on any dose of prednisone intended for antineoplastic use.

• Vaccination with a live vaccine within 28 days prior to start of study therapy, with the exception of vaccinations for coronavirus disease 2019 (COVID-19), as applicable. Live vaccination for COVID-19 should occur at least two weeks prior to cycle 1, day 1 (C1D1).

• Major surgery within four weeks of planned start of study therapy Prolongation of the QT interval corrected by Fridericia's Formula for heart rate (QTcF) greater than (>) 470 milliseconds (msec).

• Clinically significant cardiovascular disease.

• Female patient who is pregnant or lactating.

• Active second malignancy which may preclude assessment of DLT.

• Clinically significant active malabsorption syndrome including surgical resection of small intestine or other condition likely to affect gastrointestinal (GI) absorption of the orally administered study drugs.

• Active hepatitis B or C infection.

• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal) or other clinically significant active disease process.

• Active uncontrolled auto-immune cytopenia.

• Additional exclusion criteria for patients enrolled to part 2: LOXO-338 and pirtobrutinib combination

• Prior progression or intolerance to pirtobrutinib.

• Patients requiring therapeutic anticoagulation with warfarin.

• Known hypersensitivity to any component or excipient of pirtobrutinib.

• In patients with history of myocardial infarction or congestive heart failure, documented left ventricular ejection fraction (LVEF) by any method of ≤ 45 percent (%) in the 12 months prior to planned start of study treatment.

• History of uncontrolled or symptomatic arrhythmias including grade ≥ 3 arrhythmia on a prior BTK inhibitor.

• History of major bleeding on a prior BTK inhibitor.

• Current treatment with strong permeability glycoprotein (P-gp) inhibitors.