GoldiLox: This study is evaluating how safe and effective combination targeted therapy is in people with relapsed mantle cell lymphoma who have had prior treatment with a BTK inhibitorAn Open-label, Single-arm, Phase 2 Trial of GlOfitamab anD pIrtobrutinib (LOXo-305) in Patients With Mantle Cell Lymphoma and Prior Exposure to a BTK Inhibitor (GOlDiLOX)

Exclusion

1. Inability to comply with protocol mandated hospitalisations
2. For patients enrolling on the safety cohort, a history of allogeneic transplantation within 12 months of enrolment or ongoing chronic GVHD or immunosuppressive therapy.
3. Autologous SCT or CAR-T therapy within 6 weeks of enrolment
4. Active central nervous system involvement with MCL
5. Prior treatment with pirtobrutinib or demonstrated refractoriness to a CD20xCD3 bispecific antibody.
6. Have a known severe hypersensitivity to any of the excipients of pirtobrutinib, glofitamab, tocilizumab or obinutuzumab.
7. History of stroke or intracranial haemorrhage within six months of enrolment.
8. Live vaccination within 28 days of enrolment.
9. Major surgery or significant traumatic injury within 28 days of study treatment or the anticipation of major surgery during study treatment (surgical procedures for the diagnosis of lymphoma such as lymph node resection/ laparoscopy are allowed provided patient is considered fit for treatment as judged by investigator)

10. Significant cardiovascular disease defined as:

    1. Unstable angina or acute coronary syndrome within 2 months of registration
    2. History of myocardial infarction within 3 months prior to registration
    3. Documented LVEF by any method of = 40% during screening
    4. Grade 3 or higher NYHA functional classification system of heart failure
    5. Uncontrolled or symptomatic arrhythmias
11. Prolongation of the QT interval corrected for heart rate (QTcF) greater than 470 msec on at least 2/3 consecutive electrocardiograms (ECGs), and mean QTcF greater than 470 msec on all 3 ECGs, during Screening. QTcF is calculated using Fridericia's Formula (QTcF): QTcF euqal to QT/(RR0.33) Correction of suspected drug-induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switching to another drug not known to be associated with QTcF prolongation. Correction for underlying bundle branch block (BBB) allowed. Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias
12. Known human immunodeficiency virus (HIV) infection

13. Known active HBV or HCV infection based on criteria below:

    1. HBV: Patients with positive HbsAg are excluded. Patients with positive hepatitis B core antibody antiHBc and negative HbsAg require negative hepatitis B PCR before enrolment and must be treated with antiviral therapy. Patients who are hepatitis B PCR positive will be excluded.
    2. HCV: If positive hepatitis C antibody, patient will need to have a negative hepatitis C RNA before enrolment. Patients who are hepatitis C RNA positive will be excluded.
14. Known active CMV infection. Unknown or negative status are eligible.
15. Pregnancy, lactation or plan to breastfeed during the study or within 6 months of the last dose of study treatment.
16. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of pirtobrutinib.
17. Evidence of other clinically significant uncontrolled condition(s) including but not limited to, uncontrolled systemic bacterial, viral, fungal or parasitic 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.
18. Active uncontrolled auto-immune cytopenia (e.g., AIHA, ITP) for which new therapy was introduced or existing therapy was escalated within the 4 weeks prior to study enrolment to maintain adequate blood counts, unless auto-immune cytopenias are secondary to MCL
19. Active second malignancy unless in remission and with life expectancy greater than 2 years.
20. Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or strong P-gp inhibitors.
21. Patients requiring therapeutic anticoagulation with warfarin or another vitamin K antagonist.