Mantle cell lymphoma MedDRA version: 20.0 Level: LLT Classification code 10026799 Term: Mantle cell lymphoma NOS System Organ Class: 100000004864
Conditions
Sponsors
Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company
Eligibility
Sex/Gender
All
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: -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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: • Current suspected or confirmed active central nervous system (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 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 |
|---|---|
| Main Objective: To compare PFS of pirtobrutinib as monotherapy (Arm A) to Investigator choice of covalent BTK inhibitor monotherapy (Arm B) in patients with previously treated MCL;Secondary Objective: -To compare efficacy of pirtobrutinib as monotherapy (Arm A) to Investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms -To evaluate the safety and tolerability of each treatment arm -To evaluate the patient-reported outcomes;Primary end point(s): Assessed by independent review committee (IRC) • PFS per Lugano criteria;Timepoint(s) of evaluation of this end point: The time from the date of randomization until PD or death from any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Assessed by both Investigator assessment and IRC • ORR per Lugano criteria • DOR per Lugano criteria Assessed by Investigator assessment: • PFS per Lugano criteria • OS • Event-free survival (EFS) • Time to treatment failure (TTF) • Time to next treatment (TTNT) • Progression-free survival 2 (PFS2) Incidence and severity of SAEs, 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 • Time to worsening (TTW) of MCL-related symptoms;Timepoint(s) of evaluation of this end point: ORR - achieving a BOR of CR or PR DOR - earlier of the documentation of definitive PD or death from any cause PFS - PD or death from any cause, whichever occurs first OS - death from any cause EFS - date of PD or start of subsequent anticancer therapy for MCL or withdrawal from treatment due to toxicity or death, whichever occurs first TTF - composite endpoint, discontinuation of treatment for any reason TTNT - date of subsequent anticancer therapy for MCL, or death, whichever occurs first PFS 2 - disease progression on next line treatment, or death from any cause | — |
Countries
Australia, Austria, Belgium, Canada, China, Czechia, Czech Republic, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Portugal, Russian Federation, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactMedical and Scientific Services
IQVIA RDS GmbH
Outcome results
None listed