search
Back to results

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

Primary Purpose

Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-cell Marginal Zone, Lymphoma, Non-Hodgkin

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LOXO-338
Pirtobrutinib
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Lymphocytic, Chronic, B-Cell focused on measuring BTKi, Hematologic disease, Small lymphocytic lymphoma, BCL-2 inhibitor, CLL, SLL, NHL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The University of Arizona Cancer Center
  • City of Hope National Medical Center
  • University of California San Francisco, Medical Center at Paranassus
  • Mayo Clinic in Florida
  • Sylvester Comprehensive Cancer Center
  • Emory University
  • Indiana Blood & Marrow Transplantation (IBMT)
  • University of Kansas Medical Center
  • Tufts Medical Center
  • Mayo Clinic
  • Memorial Sloan Kettering Cancer Center
  • Swedish Medical Center
  • Medical College of Wisconsin
  • L'Institut Universitaire du Cancer de Toulouse Oncopole
  • Centre Hospitalier Lyon Sud
  • CHRU de Montpellier-Hopital St Eloi
  • Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu
  • Institut Curie
  • Centre hospitalier universitaire de Haut Leveque
  • IRCCS - AOU di Bologna
  • Centrum Medyczne Pratia Poznan
  • Pratia MCM Krakow
  • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

LOXO-338 (Monotherapy)

LOXO-338 + Pirtobrutinib (Combination)

Arm Description

LOXO-338 administered orally.

LOXO-338 administered orally in combination with pirtobrutinib

Outcomes

Primary Outcome Measures

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)
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
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)

Secondary Outcome Measures

Part 1 - To characterize the pharmacokinetics (PK) properties of LOXO-338: Area under the plasma concentration versus time curve (AUC)
PK: AUC of LOXO-338
Part 1 - To characterize the PK properties of LOXO-338: Maximum drug concentration (Cmax)
PK: Cmax of LOXO-338
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on overall response rate (ORR)
ORR
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on progression-free survival (PFS)
PFS
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on time-to-progression (TTP)
TTP
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on duration of response (DOR)
DOR
Part 2 - To characterize the pharmacokinetics (PK) properties of LOXO-338 in combination with pirtobrutinib: Area under the plasma concentration versus time curve (AUC)
PK: AUC of LOXO-338 alone and in combination with pirtobrutinib
Part 2 - To characterize the PK properties of LOXO-338 and in combination with pirtobrutinib: Maximum drug concentration (Cmax)
PK: Cmax of LOXO-338 alone and in combination with pirtobrutinib
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on overall response rate (ORR)
ORR
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on progression-free survival (PFS)
PFS
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on time-to-progression (TTP)
TTP
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on duration of response (DOR)
DOR

Full Information

First Posted
August 25, 2021
Last Updated
May 30, 2023
Sponsor
Eli Lilly and Company
Collaborators
Loxo Oncology, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT05024045
Brief Title
Study of Oral LOXO-338 in Patients With Advanced Blood Cancers
Official Title
A Phase 1 Study of Oral LOXO-338, a Selective BCL-2 Inhibitor, in Patients With Advanced Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 30, 2021 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
Collaborators
Loxo Oncology, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
316 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LOXO-338 (Monotherapy)
Arm Type
Experimental
Arm Description
LOXO-338 administered orally.
Arm Title
LOXO-338 + Pirtobrutinib (Combination)
Arm Type
Experimental
Arm Description
LOXO-338 administered orally in combination with pirtobrutinib
Intervention Type
Drug
Intervention Name(s)
LOXO-338
Other Intervention Name(s)
LY3847429
Intervention Description
Oral
Intervention Type
Drug
Intervention Name(s)
Pirtobrutinib
Other Intervention Name(s)
LOXO-305, LY3527727
Intervention Description
Oral
Primary Outcome Measure Information:
Title
Part 1 - To determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of oral LOXO-338
Description
Measured by the number of patients with dose-limiting toxicities (DLTs)
Time Frame
Cycle 1 (28 Days)
Title
Part 1 - To determine the effect of LOXO-338 on response rates
Description
Measured by the appropriate disease specified response criteria as appropriate to tumor type
Time Frame
Estimated up to 2 years
Title
Part 2 - To determine the safety and tolerability of LOXO-338 when given in combination with pirtobrutinib
Description
Measured by the number of patients with dose-limiting toxicities (DLTs)
Time Frame
Cycle 2 (28 Days)
Secondary Outcome Measure Information:
Title
Part 1 - To characterize the pharmacokinetics (PK) properties of LOXO-338: Area under the plasma concentration versus time curve (AUC)
Description
PK: AUC of LOXO-338
Time Frame
Predose up to 24 hours postdose
Title
Part 1 - To characterize the PK properties of LOXO-338: Maximum drug concentration (Cmax)
Description
PK: Cmax of LOXO-338
Time Frame
Predose up to 24 hours postdose
Title
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on overall response rate (ORR)
Description
ORR
Time Frame
Estimated up to 2 years
Title
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on progression-free survival (PFS)
Description
PFS
Time Frame
Estimated up to 2 years
Title
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on time-to-progression (TTP)
Description
TTP
Time Frame
Estimated up to 2 years
Title
Part 1 - To assess preliminary antitumor activity of LOXO-338 based on duration of response (DOR)
Description
DOR
Time Frame
Estimated up to 2 years
Title
Part 2 - To characterize the pharmacokinetics (PK) properties of LOXO-338 in combination with pirtobrutinib: Area under the plasma concentration versus time curve (AUC)
Description
PK: AUC of LOXO-338 alone and in combination with pirtobrutinib
Time Frame
Predose up to 24 hours postdose
Title
Part 2 - To characterize the PK properties of LOXO-338 and in combination with pirtobrutinib: Maximum drug concentration (Cmax)
Description
PK: Cmax of LOXO-338 alone and in combination with pirtobrutinib
Time Frame
Predose up to 24 hours postdose
Title
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on overall response rate (ORR)
Description
ORR
Time Frame
Estimated up to 2 years
Title
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on progression-free survival (PFS)
Description
PFS
Time Frame
Estimated up to 2 years
Title
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on time-to-progression (TTP)
Description
TTP
Time Frame
Estimated up to 2 years
Title
Part 2 - To assess preliminary antitumor activity of LOXO-338 alone and in combination with pirtobrutinib based on duration of response (DOR)
Description
DOR
Time Frame
Estimated up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Pauff, MD; PhD
Organizational Affiliation
Loxo Oncology, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
The University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-0269
Country
United States
Facility Name
University of California San Francisco, Medical Center at Paranassus
City
San Francisco
State/Province
California
ZIP/Postal Code
94117
Country
United States
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Indiana Blood & Marrow Transplantation (IBMT)
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
University of Kansas Medical Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905-0002
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Swedish Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
L'Institut Universitaire du Cancer de Toulouse Oncopole
City
Toulouse
State/Province
Cedex 9
ZIP/Postal Code
31100
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre-Bénite
State/Province
Cedex
ZIP/Postal Code
69495
Country
France
Facility Name
CHRU de Montpellier-Hopital St Eloi
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Facility Name
Centre Hospitalier Universitaire de Nantes - L' Hopital l'hôtel-Dieu
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Institut Curie
City
Paris
ZIP/Postal Code
75248
Country
France
Facility Name
Centre hospitalier universitaire de Haut Leveque
City
Pessac Cedex
ZIP/Postal Code
33604
Country
France
Facility Name
IRCCS - AOU di Bologna
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Centrum Medyczne Pratia Poznan
City
Skorzewo
State/Province
Poznan
ZIP/Postal Code
60 185
Country
Poland
Facility Name
Pratia MCM Krakow
City
Krakow
ZIP/Postal Code
30-510
Country
Poland
Facility Name
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://trials.lillytrialguide.com/en-US/trial/3WoOdectArUAmQZPkKcclh?nickname=J3N-OX-JZRA
Description
Study of Oral LOXO-338 in Patients with Advanced Blood Cancers

Learn more about this trial

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

We'll reach out to this number within 24 hrs