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

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05024045
Collaborator
Loxo Oncology, Inc. (Industry)
286
Enrollment
3
Locations
2
Arms
30
Anticipated Duration (Months)
95.3
Patients Per Site
3.2
Patients Per Site Per Month

Study Details

Study Description

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).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
286 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study of Oral LOXO-338, a Selective BCL-2 Inhibitor, in Patients With Advanced Hematologic Malignancies
Actual Study Start Date :
Sep 30, 2021
Anticipated Primary Completion Date :
Apr 1, 2024
Anticipated Study Completion Date :
Apr 1, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: LOXO-338 (Monotherapy)

LOXO-338 administered orally.

Drug: LOXO-338
Oral
Other Names:
  • LY3847429
  • Experimental: LOXO-338 + Pirtobrutinib (Combination)

    LOXO-338 administered orally in combination with pirtobrutinib

    Drug: LOXO-338
    Oral
    Other Names:
  • LY3847429
  • Drug: Pirtobrutinib
    Oral
    Other Names:
  • LOXO-305
  • LY3527727
  • Outcome Measures

    Primary Outcome Measures

    1. Part 1 - To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of oral LOXO-338 [Cycle 1 (28 Days)]

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

    2. Part 2 - To determine the safety and tolerability of LOXO-338 when given in combination with pirtobrutinib [Cycle 2 (28 Days)]

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

    Secondary Outcome Measures

    1. 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]

      PK: AUC of LOXO-338

    2. Part 1 - To characterize the PK properties of LOXO-338: Maximum drug concentration (Cmax) [Predose up to 24 hours postdose]

      PK: Cmax of LOXO-338

    3. Part 1 - To assess preliminary antitumor activity of LOXO-338 based on overall response rate (ORR) [Estimated up to 2 years]

      ORR

    4. Part 1 - To assess preliminary antitumor activity of LOXO-338 based on progression-free survival (PFS) [Estimated up to 2 years]

      PFS

    5. Part 1 - To assess preliminary antitumor activity of LOXO-338 based on time-to-progression (TTP) [Estimated up to 2 years]

      TTP

    6. Part 1 - To assess preliminary antitumor activity of LOXO-338 based on duration of response (DOR) [Estimated up to 2 years]

      DOR

    7. Part 2 - To characterize the pharmacokinetics (PK) properties of LOXO-338 in combination with pirtobrutinib: Area under the plasma concentration versus time curve (AUC) [Predose up to 24 hours postdose]

      PK: AUC of LOXO-338 alone and in combination with pirtobrutinib

    8. Part 2 - To characterize the PK properties of LOXO-338 and in combination with pirtobrutinib: Maximum drug concentration (Cmax) [Predose up to 24 hours postdose]

      PK: Cmax of LOXO-338 alone and in combination with pirtobrutinib

    9. Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on overall response rate (ORR) [Estimated up to 2 years]

      ORR

    10. Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on progression-free survival (PFS) [Estimated up to 2 years]

      PFS

    11. Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on time-to-progression (TTP) [Estimated up to 2 years]

      TTP

    12. Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on duration of response (DOR) [Estimated up to 2 years]

      DOR

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    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 0-2.

    • 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.

    Exclusion Criteria:
    • Prior to identification of the 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

    • 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, with the exception of vaccinations for coronavirus disease 2019 (COVID-19), as applicable. Live vaccination for COVID-19 should occur at least two weeks prior to cycle 1, day 1 (C1D1).

    • 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 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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Sylvester Comprehensive Cancer CenterMiamiFloridaUnited States33136
    2Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
    3Medical College of WisconsinMilwaukeeWisconsinUnited States53226

    Sponsors and Collaborators

    • Eli Lilly and Company
    • Loxo Oncology, Inc.

    Investigators

    • Study Director: James Pauff, MD; PhD, Loxo Oncology, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT05024045
    Other Study ID Numbers:
    • LOXO-BCL-20001
    • 2021-000060-30
    • J3N-OX-JZRA
    First Posted:
    Aug 27, 2021
    Last Update Posted:
    Nov 22, 2021
    Last Verified:
    Nov 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Eli Lilly and Company
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 22, 2021