Study of Oral LOXO-338 in Patients With Advanced Blood Cancers
Purpose
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.
Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Lymphoma, B-cell Marginal Zone
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- B-cell Lymphoma
- Waldenstrom Macroglobulinemia
- Lymphoma, Mantle-Cell
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
- 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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental LOXO-338 (Monotherapy) |
LOXO-338 administered orally. |
|
|
Experimental LOXO-338 + Pirtobrutinib (Combination) |
LOXO-338 administered orally in combination with pirtobrutinib |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- Eli Lilly and Company
Study Contact
Detailed Description
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).