A Phase 3 Open-Label, Randomized Study of LOXO-305 versus Investigator Choice of BTK Inhibitor in Patients with Previously Treated BTK Inhibitor Naïve Mantle Cell Lymphoma (BRUIN MCL-321)
- Conditions
- Mantle Cell LymphomaMCL10025320
- Registration Number
- NL-OMON54133
- Lead Sponsor
- oxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 8
• 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
• 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Assessed by independent review committee (IRC)<br /><br>• PFS per Lugano criteria</p><br>
- Secondary Outcome Measures
Name Time Method <p>Assessed by both investigator assessment and IRC<br /><br>• Overall response rate (ORR) per Lugano criteria<br /><br>• Duration of response (DOR) per Lugano criteria<br /><br>Assessed by investigator assessment:<br /><br>• PFS per Lugano criteria<br /><br>• OS<br /><br>• EFS<br /><br>• TTF<br /><br>• TTNT<br /><br>• PFS2<br /><br>Incidence and severity of serious adverse events (SAEs), adverse events<br /><br>(AEs), deaths, and clinical laboratory abnormalities per Common<br /><br>Terminology<br /><br>Criteria for Adverse Events (CTCAE v5.0)<br /><br>• Comparative tolerability: proportion of time with high side-effect<br /><br>burden<br /><br>• TTW of MCL-related symptoms</p><br>