A clinical study to assess the effectiveness and safety of LOXO-305 compared to standard of care treatment chosen by the Investigator in patients with previously treated Mantle Cell Lymphoma

Phase 1

• Conditions: Mantle cell lymphoma; MedDRA version: 20.0Level: LLTClassification code 10026799Term: Mantle cell lymphoma NOSSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004553-72-FR
• Lead Sponsor: oxo Oncology, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-02-22
• Last Update Posted: 24 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 500

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 on radiologic assessment as defined by Lugano criteria: at least one nodal lesion (> 1.5 cm in long axis) or extra-nodal 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.
• ECOG 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

• 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 on at least 2/3 consecutive electrocardiograms (ECGs), and mean QTcF > 470 msec on all 3 ECGs, 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, lactation or plan to breastfeed during the study or within 30 days 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 and non-metastatic breast or prostate cancer where hormonal therapy is being continued as standard of care are allowed.

Prior/Concomitant Therapy
• Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors.
Because of their effect on CYP3A4, use of any of the following within 3 days of study therapy start or planned use during study participation is prohibited: grapefruit or grapefruit products, Seville oranges or products from Seville oranges, star fruit.
• Steroid use with anti-neoplastic intent within 7 days of study drug initiation.
• Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist.
• Vaccination with live vaccine within 28 days prior to randomization.

• Have a known hypersensitivity to any of the excipients of LOXO-305 or to the intended covalent BTK inhibitor if randomized to control arm.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: -To compare efficacy of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms<br>-To evaluate the safety and tolerability of each treatment arm<br>-To evaluate the patient-reported outcomes;Primary end point(s): Assessed by independent review committee (IRC)<br>• 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.;Main Objective: To compare progression-free survival (PFS) of LOXO-305 as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm<br>B) in patients with previously treated mantle cell lymphoma (MCL)