Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Bita Fakhri

Description

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.

Official Title

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

Details

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).

Keywords

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 Lymphoma, B-Cell Leukemia, Lymphoid LOXO-338 Pirtobrutinib LOXO-338 (Monotherapy)

Eligibility

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:
  • Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocyticleukemia, or Hodgkin lymphoma
  • Transformed low grade lymphoma
  • Burkitt or Burkitt-like lymphoma
  • Diffuse large B-cell lymphoma
  • AL amyloidosis
  • 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.
  • 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.

Locations

  • University of California San Francisco, Medical Center at Paranassus accepting new patients
    San Francisco California 94117 United States
  • Swedish Medical Center accepting new patients
    Seattle Washington 98104 United States

Lead Scientist at UCSF

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Eli Lilly and Company
ID
NCT05024045
Phase
Phase 1 research study
Study Type
Interventional
Participants
Expecting 316 study participants
Last Updated