for people ages 18 years and up (full criteria)
study started
estimated completion



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.

Official Title

A Phase 1 Study of Oral LOXO-338, a Selective BCL-2 Inhibitor, in Patients With Advanced Hematologic Malignancies


This study will be conducted in 2 parts. Part 1 will evaluate LOXO-338 as monotherapy. If safety and initial evidence of efficacy of LOXO-338 monotherapy are confirmed, part 2 will evaluate the combination of LOXO-338 with the highly selective, noncovalent Bruton's tyrosine kinase (BTK) inhibitor, pirtobrutinib (LOXO-305).


Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-cell Marginal Zone, Lymphoma, Non-Hodgkin, Multiple Myeloma, B-cell Lymphoma, Waldenstrom Macroglobulinemia, Lymphoma, Mantle-Cell, BTKi, Hematologic disease, Small lymphocytic lymphoma, BCL-2 inhibitor, CLL, SLL, NHL, Lymphoma, Non-Hodgkin Lymphoma, Lymphoid Leukemia, Mantle-Cell Lymphoma, LOXO-338, Pirtobrutinib, LOXO-338 (Monotherapy)


You can join if…

Open to people ages 18 years and up

  • 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 0-1.
  • 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.
  • Additional Inclusion Criteria for Patients with AL Amyloidosis
    • In Part 1 Dose Expansion, patients with AL amyloidosis are eligible based on prior detection of primary systemic light-chain amyloidosis.
    • Must have measurable disease of AL amyloidosis.
    • Prior local fluorescence in-situ hybridization (FISH) testing results for t(11;14) are required to be submitted prior to enrollment.

You CAN'T join if...

  • Prior to identification of an appropriate RP2D (Dose Expansion) of LOXO-338, a history of known, active or suspected:
  • 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.
  • 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 with AL Amyloidosis (Part 1 Dose-Expansion)
    • Previous or current diagnosis of symptomatic MM.
    • Heart failure that, in the opinion of the Investigator, is on the basis of ischemic heart disease.
    • Supine systolic blood pressure < 90 mmHg, or symptomatic orthostatic hypotension in the absence of volume depletion.
    • N-terminal pro hormone natriuretic peptide (NT-proBNP) > 8500 ng/L (or BNP > 700 ng/L if NT-proBNP is not available by local or central testing).
  • 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.


  • University of California San Francisco, Medical Center at Paranassus
    San Francisco California 94117 United States
  • City of Hope National Medical Center
    Duarte California 91010-0269 United States


in progress, not accepting new patients
Start Date
Completion Date
Eli Lilly and Company
Phase 1 research study
Study Type
Expecting 316 study participants
Last Updated