Study of Oral LOXO-338 in Patients With Advanced Blood Cancers

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Prashant Kapoor, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Han Tun, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions