Mantle Cell Lymphoma MCL
Conditions
Interventions
Subjects will be randomized 1:1 to Arm A (LOXO-305) versus Arm B
(investigator's choice of BTK inhibitor).
Subjects enrolled in Arm A receive 200mg LOXO-305 each day and subjects
enrolled in Arm B r
Sponsors
Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: • At least 18 years of age • Confirmed diagnosis by local laboratory of MCL with documentation of overexpression of cyclin D1 with at least one B-cell marker (e.g., CD19, CD20, or PAX5) and/or t (11;14), by cytogenetics, fluorescent in situ hybridization (FISH) or polymerase chain reaction. • Previously treated with at least one prior line of systemic therapy for MCL. •Measurable disease by PET-CT and/or CT/MRI as defined by Lugano criteria and aligned with protocol imaging requirements: - PET-CT: FDG (fluorodeoxyglucose) avid lymphoma lesion - at least one nodal lesion (> 1.5 cm in long axis) or extranodal lesion (> 1.0 cm in long axis) measurable in 2 dimensions, not previously radiated (unless progression has been radiographically documented following radiation therapy). • Documented evidence of radiographically and/or histologically confirmed PD on the most recent line of therapy or relapse prior to study enrollment. • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 • Adequate organ function • Must have life expectancy of at least 3 months
Exclusion criteria
Exclusion criteria: • Current suspected or confirmed active CNS involvement with MCL or previous CNS involvement. • Prior treatment with an approved or investigational BTK inhibitor. • Major surgery within 4 weeks prior to randomization. • History of bleeding diathesis. • History of stroke or intracranial hemorrhage within 6 months of randomization. • History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified T-cell (CAR-T) therapy within 60 days of randomization. • Significant cardiovascular disease. • Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec during Screening. • Known human immunodeficiency virus (HIV) infection, regardless of CD4 count. • Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. • Known active cytomegalovirus (CMV) infection. Unknown or negative status are eligible. • Pregnancy during the study or within 3 months of the last dose of study treatment. • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drug. • Evidence of other clinically significant uncontrolled condition(s) including but not limited to, uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator and medical monitor may pose a risk for patient participation. Screening for chronic conditions is not required. •History of second malignancy unless in remission for at least 2 years; in-situ carcinomas not requiring treatment intervention, , non-melanoma skin cancer curatively treated, nonmetastatic breast, or nonmetastatic prostate cancer where hormonal therapy is being continued as standard of care are allowed. Prior/Concomitant Therapy • Ongoing chronic treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers which cannot be stopped within 3-5 half-lives of the CYP3A inhibitor therapy prior to start of study drug treatment. Because of their effect on CYP3A4, use of any of the following within 3 days of study therapy start is prohibited: Grapefruit or grapefruit products, Seville oranges or products from Seville oranges, Star fruit or star fruit products. • Steroid use with antineoplastic intent within 7 days of study drug initiation. • Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist. • Vaccination with a live vaccine within 28 days prior to randomization. • Have a known hypersensitivity to any of the excipients of pirtobrutinib or to the intended covalent BTK inhibitor if randomized to control arm. •Laction, or plan to breastfeed during the study or within 2 weeks of the last dose of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assessed by independent review committee (IRC) • PFS per Lugano criteria | — |
Secondary
| Measure | Time frame |
|---|---|
| Assessed by both investigator assessment and IRC • Overall response rate (ORR) per Lugano criteria • Duration of response (DOR) per Lugano criteria Assessed by investigator assessment: • PFS per Lugano criteria • OS • EFS • TTF • TTNT • PFS2 Incidence and severity of serious adverse events (SAEs), adverse events (AEs), deaths, and clinical laboratory abnormalities per Common Terminology Criteria for Adverse Events (CTCAE v5.0) • Comparative tolerability: proportion of time with high side-effect burden • TTW of MCL-related symptoms | — |
Countries
Netherlands
Outcome results
None listed