New pill shows promise for Hard-to-Treat blood cancers

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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.