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

NCT05024045 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: 182582021-000060-30J3N-OX-JZRALOXO-BCL-20001
• Study Type: interventional
• Target: 316
• Locations: 4 countries
• Sites: 23

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.

Conditions

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

Keywords

BTKi; Hematologic disease; Small lymphocytic lymphoma; BCL-2 inhibitor; CLL; SLL; NHL

Outcome Measures

Primary Outcomes (3)

• Part 1 - To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of oral LOXO-338

  Measured by the number of patients with dose-limiting toxicities (DLTs)

  Cycle 1 (28 Days)

• Part 1 - To determine the effect of LOXO-338 on response rates

  Measured by the appropriate disease specified response criteria as appropriate to tumor type

  Estimated up to 2 years

• Part 2 - To determine the safety and tolerability of LOXO-338 when given in combination with pirtobrutinib

  Measured by the number of patients with dose-limiting toxicities (DLTs)

  Cycle 2 (28 Days)

Secondary Outcomes (12)

• Part 1 - To characterize the pharmacokinetics (PK) properties of LOXO-338: Area under the plasma concentration versus time curve (AUC)

  Predose up to 24 hours postdose

• Part 1 - To characterize the PK properties of LOXO-338: Maximum drug concentration (Cmax)

  Predose up to 24 hours postdose

• Part 1 - To assess preliminary antitumor activity of LOXO-338 based on overall response rate (ORR)

  Estimated up to 2 years

• Part 1 - To assess preliminary antitumor activity of LOXO-338 based on progression-free survival (PFS)

  Estimated up to 2 years

• Part 1 - To assess preliminary antitumor activity of LOXO-338 based on time-to-progression (TTP)

  Estimated up to 2 years

Study Arms (2)

LOXO-338 (Monotherapy)

EXPERIMENTAL

LOXO-338 administered orally.

Drug: LOXO-338

LOXO-338 + Pirtobrutinib (Combination)

EXPERIMENTAL

LOXO-338 administered orally in combination with pirtobrutinib

Drug: LOXO-338; Drug: Pirtobrutinib

Interventions

LOXO-338 DRUG

Oral

Also known as: LY3847429

LOXO-338 (Monotherapy); LOXO-338 + Pirtobrutinib (Combination)

Pirtobrutinib DRUG

Oral

Also known as: LOXO-305, LY3527727

LOXO-338 + Pirtobrutinib (Combination)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (23)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

City of Hope National Medical Center

Duarte, California, 91010-0269, United States

Location

University of California San Francisco, Medical Center at Paranassus

San Francisco, California, 94117, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana Blood & Marrow Transplantation (IBMT)

Indianapolis, Indiana, 46237, United States

Location

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905-0002, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

L'Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, Cedex 9, 31100, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, Cedex, 69495, France

Location

CHRU de Montpellier-Hopital St Eloi

Montpellier, 34295, France

Location

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

Nantes, 44093, France

Location

Institut Curie

Paris, 75248, France

Location

Centre hospitalier universitaire de Haut Leveque

Pessac, 33604, France

Location

IRCCS - AOU di Bologna

Bologna, 40138, Italy

Location

Centrum Medyczne Pratia Poznan

Skorzewo, Poznan, 60 185, Poland

Location

Pratia MCM Krakow

Krakow, 30-510, Poland

Location

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

Warsaw, 02-781, Poland

Location

Related Publications (1)

• 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.

  PMID: 40000354 DERIVED

Related Links

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

MeSH Terms

Conditions

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

Interventions

pirtobrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: August 27, 2021
• Study Start: September 30, 2021
• Primary Completion: June 14, 2023
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (13); FR (6); IT (1); PL (3)