B-cell Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-cell Marginal Zone, Lymphoma, Mantle-Cell, Lymphoma, Non-Hodgkin, Multiple Myeloma, Waldenstrom Macroglobulinemia
Conditions
Keywords
BTKi, Hematologic disease, Small lymphocytic lymphoma, BCL-2 inhibitor, CLL, SLL, NHL
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).
Interventions
DRUGLOXO-338
Oral
DRUGPirtobrutinib
Oral
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 0-1. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Part 1 - To determine the effect of LOXO-338 on response rates | Estimated up to 2 years | 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 | Cycle 2 (28 Days) | Measured by the number of patients with dose-limiting toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Part 1 - To assess preliminary antitumor activity of LOXO-338 based on overall response rate (ORR) | Estimated up to 2 years | ORR |
| Part 1 - To assess preliminary antitumor activity of LOXO-338 based on progression-free survival (PFS) | Estimated up to 2 years | PFS |
| Part 1 - To assess preliminary antitumor activity of LOXO-338 based on time-to-progression (TTP) | Estimated up to 2 years | TTP |
| Part 1 - To assess preliminary antitumor activity of LOXO-338 based on duration of response (DOR) | Estimated up to 2 years | 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) | Predose up to 24 hours postdose | 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) | Predose up to 24 hours postdose | 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) | Estimated up to 2 years | ORR |
| 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 |
| 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 |
| 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 |
Countries
France, Italy, Poland, United States
Contacts
STUDY_DIRECTORCall 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
Outcome results
None listed