A Trial of Polatuzumab Vedotin, Obinutuzumab and Glofitamab As a Peri-CAR-T Cell Treatment Strategy in Large B-cell Lymphoma

NCT06071871 | Recruiting Phase 2 DMC

• 2 other identifiers: UCL/1508622022-003727-17
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 5

Brief Summary

The PORTAL study will test a new combination of drugs (glofitamab, polatuzumab vedotin and obinutuzumab) in patients with large B-cell lymphoma (LBCL) that has come back (relapsed) or not responded to previous treatment. It will determine how safe and effective the combination of these cancer drugs is in treating LBCL before and after CAR-T cell therapy.

Conditions

Large B-cell Lymphoma

Keywords

Glofitamab; Polatuzumab vedotin; Obinutuzumab; Bridging therapy; Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Part 1: Overall Response Rate (ORR) to Pola-Glofit as bridging prior to CAR-T cell infusion

  To determine the efficacy of Pola-Glofit as bridging treatment to CAR-T cell therapy in patients with r/r LBCL. ORR i.e. the proportion of patients achieving response (Complete Metabolic Response or Partial Metabolic Response) 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.

  At Cycle 2 Day 14-19 (or earlier) (each cycle is 21 days)

• Part 2: Progression Free Survival (PFS) at 6 months

  To determine the efficacy of Pola-Glofit in patients with LBCL who have failed to achieve CMR, or progressed after CAR-T cell therapy. PFS at 6 months will be analysed using Kaplan-Meier survival analysis, with the rate at 6 months (with 70% CI) presented. The median (if reached) and plot will also be given.

  From the date of registration at Part 2 until the date of first disease progression or death, whichever comes first, assessed up to 4 years

Secondary Outcomes (15)

• Part 1: Complete Metabolic Response (CMR) rate to Pola-Glofit as bridging prior to CAR-T cell infusion

  At Cycle 2 Day 14-19 of bridging treatment (each cycle is 21 days)

• Part 1: Overall Survival (OS) and Progression Free Survival (PFS)

  From the date of registration at Part 1 until the date of disease progression or death (PFS), or death (OS). This will be assessed from the date of registration until up to 4 years.

• Part 1: Safety and toxicity of Pola-Glofit as bridging therapy

  From registration and during Part 1 bridging treatment, until end of post-treatment safety reporting window (up to six months after last dose of obinutuzumab, plus a further 35 days after last dose of polatuzumab vedotin or last dose of glofitamab)

• Part 1: CAR-T associated toxicity post Pola-Glofit bridging following CAR-T therapy

  Between Day 0 and Day 28 following CAR-T therapy

• Part 1: Response rate post CAR-T for all infused patients

  From CAR-T infusion until 6 months post CAR-T therapy

Study Arms (2)

Part 1

EXPERIMENTAL

Patients whose large B-cell lymphoma has progressed/not responded to previous treatment and are due to start standard CAR-T therapy. All patients receive 2 cycles of glofitamab and polatuzumab vedotin (Glofit-Pola). Obinutuzumab pre-treatment is given on cycle 1 day 1. Patients have a PET-CT scan to check the response after cycle 2. If the scan shows a response and patients are still suitable for CAR-T cell therapy, patients will proceed to receive planned CAR-T therapy and will not receive further Glofit-Pola in Part 1. If not, patients can receive 4 more cycles of glofitamab and polatuzumab vedotin, and then 6 cycles of glofitamab.

Drug: Glofitamab; Drug: Polatuzumab vedotin; Drug: Obinutuzumab

Part 2

EXPERIMENTAL

Patients whose large B-cell lymphoma has progressed/not responded after standard CAR-T cell therapy. All patients receive 6 cycles of glofitamab and polatuzumab vedotin (Glofit-Pola), and then 6 cycles of glofitamab alone. Obinutuzumab pre-treatment is given on cycle 1 day 1.

Drug: Glofitamab; Drug: Polatuzumab vedotin; Drug: Obinutuzumab

Interventions

Glofitamab DRUG

Glofitamab is given intravenously at a dose of 2.5mg over 4 hours on Cycle 1 Day 8. Patients need to stay in hospital for 24 hours. Glofitamab is given intravenously at a dose of 10mg over 2 hours on Cycle 1 Day 15. (Patients may need to stay in hospital for 24 hours.) Glofitamab is given intravenously at a dose of 30mg over 2 hours on Day 1 of Cycles 2-12 (as relevant).

Also known as: Columvi

Part 1; Part 2

Polatuzumab vedotin DRUG

Polatuzumab is given intravenously at a dose of 1.8mg/kg on Cycle 1 Day 2, and then Day 1 of Cycle 2-Cycle 6.

Also known as: Polivy

Part 1; Part 2

Obinutuzumab DRUG

Obinutuzumab pre-treatment is given intravenously at a dose of 1g on Cycle 1 Day 1.

Also known as: Gazyvaro

Part 1; Part 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven CD20+ LBCL (with CD20 positivity at any timepoint) including diffuse large B cell lymphoma, high grade B cell lymphoma with MYC, BCL2 and/or BCL6 (double/triple hit lymphoma), high grade B cell lymphoma not otherwise specified (NOS), primary mediastinal B-cell lymphoma or transformed follicular lymphoma.
• Part 1: Relapsed or refractory disease and eligible for CAR T-cell therapy in the UK and in need of systemic bridging in the opinion of the local investigator.
• Part 2: Failed to achieve CMR (Deauville score 1-3) on PET scan 1-month post CAR-T or progressed at any point post CAR-T (patients in part 2 may have been previously enrolled in Part 1 and responded to Pola-Glofit bridging or be de novo patients who are naïve to this combination)
• At least one measurable target lesion
• Patient has recent archival biopsy tissue available or is willing to undergo a new biopsy.
• ECOG performance status:
• Part 1: ECOG PS 0/1
• Part 2: ECOG PS 0-2
• Life expectancy of ≥ 12 weeks
• Adequate haematological status.
• Adequate liver and renal function
• Negative test for hepatitis B, hepatitis C, HIV and SARS-CoV-2

You may not qualify if:

• Patients with known active infection
• Current ≥ Grade 2 peripheral neuropathy
• History of confirmed progressive multifocal leukoencephalopathy
• Current evidence of CNS lymphoma
• Patients with another invasive malignancy in the last 2 years
• Significant history of cardiovascular disease
• Active autoimmune disease or immune deficiency
• Severe neurological disorder
• Uncontrolled tumour-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites
• Treatment with other standard anti-cancer radiotherapy/chemotherapy including investigational therapy and targeted therapy within 4 weeks prior to cycle 1 day 1
• Prior solid organ transplantation
• Prior allogeneic stem cell transplant
• Autologous SCT within 100 days prior to cycle 1 day 1
• Any history of immune related ≥ Grade 3 adverse events

Sponsors & Collaborators

• University College, London: lead
• Hoffmann-La Roche: collaborator

Study Sites (5)

Kings College Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

University College London Hospitals NHS Foundation Trust

London, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, United Kingdom

RECRUITING

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

RECRUITING

Churchill Hospital

Oxford, United Kingdom

RECRUITING

MeSH Terms

Interventions

glofitamab; polatuzumab vedotin; obinutuzumab

Study Officials

• William Townsend

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

Central Study Contacts

PORTAL Trial Manager

CONTACT

020 7679 9860; ctc.portal@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part 1: 42 patients, Part 2: 42-57 patients (some Part 1 patients may also participate in Part 2)

Study Record Dates

• First Submitted: August 23, 2023
• First Posted: October 10, 2023
• Study Start: August 16, 2024
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2028
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5)