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

NCT ID: NCT05024045

Last Updated: 2025-04-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 316 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-30
• Study Completion Date: 2025-12-31

Brief 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.

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).

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-cell Marginal Zone; Lymphoma, Non-Hodgkin; Multiple Myeloma; B-cell Lymphoma; Waldenstrom Macroglobulinemia; Lymphoma, Mantle-Cell

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LOXO-338 (Monotherapy)

LOXO-338 administered orally.

Group Type: EXPERIMENTAL

LOXO-338

Intervention Type: DRUG

Oral

LOXO-338 + Pirtobrutinib (Combination)

LOXO-338 administered orally in combination with pirtobrutinib

Group Type: EXPERIMENTAL

LOXO-338

Intervention Type: DRUG

Oral

Pirtobrutinib

Intervention Type: DRUG

Oral

Interventions

LOXO-338

Oral

Intervention Type: DRUG

Pirtobrutinib

Oral

Intervention Type: DRUG

Other Intervention Names

LY3847429; LOXO-305; LY3527727

Eligibility Criteria

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.

• 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.

• 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).

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

The University of Arizona Cancer Center

Tucson, Arizona, United States

City of Hope National Medical Center

Duarte, California, United States

University of California San Francisco, Medical Center at Paranassus

San Francisco, California, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Emory University

Atlanta, Georgia, United States

Indiana Blood & Marrow Transplantation (IBMT)

Indianapolis, Indiana, United States

University of Kansas Medical Center

Westwood, Kansas, United States

Tufts Medical Center

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Swedish Medical Center

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

L'Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, Cedex 9, France

Centre Hospitalier Lyon Sud

Pierre-Bénite, Cedex, France

CHRU de Montpellier-Hopital St Eloi

Montpellier, , France

Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu

Nantes, , France

Institut Curie

Paris, , France

Centre hospitalier universitaire de Haut Leveque

Pessac, , France

IRCCS - AOU di Bologna

Bologna, , Italy

Centrum Medyczne Pratia Poznan

Skorzewo, Poznan, Poland

Pratia MCM Krakow

Krakow, , Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Warsaw, , Poland

Countries

United States; France; Italy; Poland

References

Kwiatek M, Murthy GSG, Hoffmann M, Tessoulin B, Danilov A, Alencar AJ, Shah NN, Ghesquieres H, Le Gouill S, Jurczak W, Han H, Yuen E, Patel V, Guo-Avrutin Y, Pauff JM, Roeker LE. A First-in-Human Phase I Study of LOXO-338, an Oral Selective Bcl-2 Inhibitor, in Patients With Advanced Hematologic Malignancies. Clin Lymphoma Myeloma Leuk. 2025 Jul;25(7):512-519. doi: 10.1016/j.clml.2025.01.018. Epub 2025 Jan 28.

Reference Type: DERIVED

PMID: 40000354 (View on PubMed)

Related Links

https://trials.lillytrialguide.com/en-US/trial/3WoOdectArUAmQZPkKcclh?nickname=J3N-OX-JZRA

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

Other Identifiers

2021-000060-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

J3N-OX-JZRA

Identifier Type: OTHER

Identifier Source: secondary_id

LOXO-BCL-20001

Identifier Type: OTHER

Identifier Source: secondary_id

18258

Identifier Type: -

Identifier Source: org_study_id