A phase II trial of polatuzumab vedotin, obinutuzumab and glofitamab as a peri-CAR-T cell treatment strategy in large B-cell lymphoma (PORTAL)

Research summary

The overall aim is: Part 1: To determine the efficacy of Pola-Glofit as bridging treatment to CAR-T cell therapy in patients with relapsed or refractory large B cell lymphomas. Part 2: To determine the efficacy of Pola-Glofit in patients with relapsed or refractory large B cell lymphomas who have failed to achieve complete metabolic response,or progressed after CAR-T cell therapy. The primary endpoints are: Part 1: Overall response rate (ORR) (Complete Metabolic Response (CMR) and Partial Metabolic Response (PMR)) after Pola-Glofit but prior to CAR-T cell infusion,assessed by central review using the 2014 Lugano Classification. Part 2: Progression-free survival at 6 months. The secondary endpoints are: Part 1: ●Complete metabolic response (CMR) rate ●Progression-free survival (PFS) ●Overall survival (OS) ●Safety and toxicity according to CTCAE/ASTCT criteria and CAR-T associated toxicity post Pola-Glofit bridging ●Response rate (per Lugano 2014 criteria) ●Duration of response (DoR) and Duration of complete response (DoCR) ●Non-relapse mortality (NRM) Part 2: ●Safety and toxicity according to CTCAE/ASTCT ●Overall response rate (ORR) ●CR rate ●Response rate (per Lugano 2014 criteria) for patients who received Pola-Glofit bridging versus those who have not ●DOR and DoCR ●OS ●PFS ●NRM The exploratory biological studies are: Tissue samples will be taken at study entry,during and post-trial treatment to assess the composition of the tumour microenvironment and immune interactions seen with Glofit-Pola and CAR-T therapy and response to treatment. Paired biopsy analysis will inform tumour and immune infiltration and identify distinct TME signatures. Analysis involves genetic,advanced microscopic techniques,enumeration of CAR-T cells and T cell subsets. Peripheral blood samples will be taken to explore changes in quantity,composition and function of peripheral T cells and CAR-T cells. These studies in correlation with known predictive markers aim to identify treatment outcomes through the development of informative biomarkers. Methodology: Primary Objective: Part 1: ORR i.e. the proportion of patients achieving response (CMR or PMR) after Pola-Glofit bridging but prior to CAR-T cell infusion,assessed by central review as per 2014 Lugano Classification. This will be presented as a rate with a 70% confidence interval. The primary endpoint will be assessed as response on day 14-19 of cycle 2 of bridging treatment (option of earlier response assessment if cell product is earlier,between Cycle 1 Day 21 and Cycle 2 Day 14). All eligible patients who received at least one dose of study treatment will be included in this analysis. Part 2: PFS at 6 months will be analysed using Kaplan-Meier survival analysis,with the rate at 6 months (with 70% CIs) presented. The median (if reached) and plot will also be given. Time will be measured from the date of registration at Part 2 until the date of first progression (as per Lugano) or death. Patients who are alive and progression free will be censored at the date last seen. All eligible patients who received at least one dose of study treatment will be included in PFS analysis.

Principal Investigator

Dr Kushani Ediriwickrema

Contact us

Email: Latephasehaematology@ouh.nhs.uk

IRAS number

1007177