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

  • End date
    Apr 23, 2024
  • participants needed
  • sponsor
    Eli Lilly and Company
Updated on 23 October 2022
measurable disease
bone marrow procedure


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.


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).

Condition Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-cell Marginal Zone, Lymphoma, Non-Hodgkin, Multiple Myeloma, B-cell Lymphoma, Waldenstrom Macroglobulinemia, Lymphoma, Mantle-Cell
Treatment Pirtobrutinib, LOXO-338
Clinical Study IdentifierNCT05024045
SponsorEli Lilly and Company
Last Modified on23 October 2022


Yes No Not Sure

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 0-1
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

Exclusion Criteria

Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocyticleukemia, or Hodgkin lymphoma
Transformed low grade lymphoma
Burkitt or Burkitt-like lymphoma
Prior to identification of an appropriate RP2D (Dose Expansion) of LOXO-338, a history of known, active or suspected
Multiple myeloma
Lymphoblastic lymphoma or leukemia
Posttransplant lymphoproliferative disorder
Known or suspected history of central nervous system (CNS) involvement
Diffuse large B-cell lymphoma
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
AL amyloidosis
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
Inability to take necessary uric acid lowering agents (i.e., allopurinol, rasburicase, orfebuxostat)
differentiation 4 (CD4) count. Unknown or negative status eligible
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
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
Vaccination with a live vaccine within 28 days prior to start of study therapy
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
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 major bleeding on a prior BTK inhibitor
History of uncontrolled or symptomatic arrhythmias including grade ≥ 3 arrhythmia on a prior BTK inhibitor
Current treatment with strong permeability glycoprotein (P-gp) inhibitors
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
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