This is a phase ll study of participants with untreated diffuse large B Cell lymphoma (DLBCL).
Men and women ≥ 18 years of age deemed eligible for treatment with full-dose Pola- R-CHP and possible treatment with glofitamab by the qualified investigator.
Histologic diagnosis of DLBCL and variants according to the WHO 201613 or WHO 202254 classification including DLBCL non-organ-specific (NOS), Germinal centre B-cell type, activated B-cell type, T-cell/histiocyte-rich large B-cell lymphoma, Epstein-Barr Virus (EBV) + DLBCL, Primary mediastinal/thymic large B-cell lymphoma, High grade B-cell lymphoma with myelocytomatosis oncogene (MYC) and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements, High grade B cell lymphoma NOS including lymphomas transformed from previously untreated indolent lymphomas.
Previously untreated DLBCL with the following exceptions: (a) prior radiotherapy for palliation (not localized), (b) up to 7 days of corticosteroids (prednisone 100mg/day equivalent).
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Current/past history of central nervous system (CNS) lymphoma.
Prior exposure to any anthracycline, rituximab or cluster of differentiation 3 (CD3) targeted bispecific antibody.
Prior malignancy (or any other malignancy requiring active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to < 5 years. Subjects receiving adjuvant hormonal therapy for early breast or prostate cancer are eligible.
Significant or extensive cardiovascular disease such as New York Heart Association Class III or IV cardiac disease or Objective Assessment Class C or D, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study.
Sequential
glofitamab
DrugGlofitamab 2.5 mg Cycle 3 Day 8 and 10 mg on Day 15 Cycles 3-6
To demonstrate the feasibility of a ctDNA and FDG-PET interim response adapted approach (iRAAp) for the primary therapy of DLBCL
Determine the proportion of patients that can have results available to risk adapt cycle treatment starting at cycle 3 based on interim testing (ctDNA collected immediately prior to cycle 2 of Pola-R-CHP, PET scan following cycle 2 of Pola-R-CHP ie. PET2). Treat the ctDNA low-risk patients (favourable ctDNA and PET2) with abbreviated chemotherapy (total 4 cycles of Pola-R-CHP with 2 courses of rituximab as a monotherapy). Treat the ctDNA high-risk patients (unfavourable ctDNA and/or PET2) with a novel treatment approach (complete 3 cycles of Pola-R-CHP and then start novel approach).
Event-free survival (EFS)
To evaluate the event-free survival (EFS) of an iRAAp in primary therapy of DLBCL
Incidence of treatment emergent adverse events
To evaluate the tolerability and toxicity of an iRAAp in primary therapy of DLBCL by assessing the frequency, severity, and relatedness of adverse events
Progression free survival (PFS) at 12 months and 24 months
To assess PFS at 12-months and 24-months in the whole population and both ctDNA high-risk and ctDNA low-risk response cohorts.
To evaluate changes in health-related quality of life (HRQOL)
To evaluate changes in health-related quality of life (HRQOL) through treatment and follow-up. HRQOL inclusive of three validated patient-reported outcome (PRO) instruments (FACT-Lym, FACT-Cog and EORTC QLQ-C30) that will be completed by the participant at required visits. The FACT-Lym was designed to address health-related quality-of-life issues for patients with non-Hodgkin's lymphoma (NHL), and includes both general concerns related to cancer treatments and specific concerns relevant to lymphoma. The FACT-Cog is a well-validated tool that measures cognitive complaints. The EORTC QLQ-C30 includes 30 separate questions (items) resulting in 5 functional scales (Physical Functioning, Role Functioning, Emotional Functioning, Cognitive Functioning, and Social Functioning), 1 Global Health Status scale, 3 symptom scales (Fatigue, Nausea and Vomiting, and Pain), and 6 single items (Dyspnea, Insomnia, Appetite Loss, Constipation, Diarrhea, and Financial Difficulties).
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