Glofitamab for Diffuse Large B-Cell Lymphoma

(GRAIL Trial)

Overseen By John Kuruvilla, FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Anthracyclines, Rituximab, CD3 antibodies

Disqualifiers: CNS lymphoma, Cardiovascular disease, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 18 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase ll study of participants with untreated diffuse large B Cell lymphoma (DLBCL).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that chronic use of steroids and certain other therapies are prohibited, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Glofitamab for treating diffuse large B-cell lymphoma?

Glofitamab has shown promising results in treating patients with relapsed or refractory diffuse large B-cell lymphoma, with 21% achieving complete response and 16% partial response in a real-world study. The median overall survival was 9 months, indicating potential effectiveness in a heavily pretreated group. ^{1 2 3 4 5}

Is Glofitamab safe for humans?

Glofitamab has been studied for safety in patients with diffuse large B-cell lymphoma. Some patients experienced serious side effects, including cytokine release syndrome (a severe immune reaction) and febrile neutropenia (fever with low white blood cell count), which led to deaths in a few cases. However, it has shown promise in treating heavily pretreated patients, and ongoing studies continue to evaluate its safety. ^{1 2 4 5 6}

What makes the drug Glofitamab unique for treating diffuse large B-cell lymphoma?

Glofitamab is unique because it is a bispecific antibody that engages T cells to attack cancer cells, specifically targeting CD20 on B cells and CD3 on T cells. This mechanism is different from traditional chemotherapy and offers a novel approach for patients who have not responded to other treatments. ^{1 2 3 4 5}

Research Team

John Kuruvilla, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

This trial is for adults with untreated Diffuse Large B-Cell Lymphoma who can undergo full-dose Pola-R-CHP and possibly glofitamab treatment. They must have a measurable mass, normal heart function, and agree to use effective contraception. Exclusions include drug or alcohol abuse, hypersensitivity to study drugs, other cancers requiring active treatment (with some exceptions), significant cardiovascular disease, uncontrolled diseases like diabetes or autoimmune disorders, active infections including HIV unless stable on therapy.

Inclusion Criteria

I am 18 or older and eligible for Pola-R-CHP and glofitamab treatment.

I have been diagnosed with a specific type of aggressive lymphoma.

I am using or willing to use effective birth control during and after the treatment.

Exclusion Criteria

I have been treated with drugs like anthracycline, rituximab, or CD3 targeted therapy.

I have no active cancer except for certain skin cancers, in situ cervical cancer, or any cancer I've been free from for 2+ years.

I do not have an active infection and have not been hospitalized for an infection or treated with IV antibiotics in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pola-R-CHP chemotherapy for 6 cycles, each 21 days in length, with risk-adapted modifications based on interim ctDNA and FDG-PET assessments

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with routine assessments including laboratory testing and imaging studies

24 months

Every 3 months (in-person), imaging every 6 months

Treatment Details

Interventions

• Glofitamab

Trial Overview The GRAIL trial is testing the feasibility of using Glofitamab in treating DLBCL patients. It's a phase II study that includes interim assessments with FDG PET scans and ctDNA analysis to optimize primary therapy based on individual responses.

Participant Groups

Group I: Pola-R-CHP and glofitamab Experimental Treatment 1 Intervention

High-risk group: Cycle 3-6 polatuzumab vedotin 1.8 mg/kg, cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 on day 1, prednisone 100 mg daily days 1-5, rituximab 375 mg/m2 within 72 hours of polatuzumab vedotin and Glofitamab 2.5 mg Cycle 3 Day 8 and 10 mg on Day 15 Cycles 3-6

Group II: Pola-R-CHP Active Control 1 Intervention

Protocol induction: Cycle 1-2 Low-risk group: Cycle 3-4 polatuzumab vedotin 1.8 mg/kg, cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 on day 1, prednisone 100 mg daily days 1-5, and rituximab 375 mg/m2 within 72 hours of polatuzumab vedotin Cycle 5-6 rituximab 375 mg/m2 on day 1 of cycle 5 and cycle 6

Glofitamab is already approved in United States for the following indications:

Approved in United States as COLUMVI for:

• Relapsed or refractory diffuse large B-cell lymphoma not otherwise specified (DLBCL), or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

Glofitamab, a bispecific monoclonal antibody targeting CD20 and CD3, was conditionally approved in Canada on March 25, 2023, for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have undergone multiple prior therapies and are ineligible for CAR T-cell therapy.

The drug is currently under regulatory review in the EU and USA, with ongoing clinical development as both a standalone treatment and in combination with other therapies for non-Hodgkin lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab: First Approval. Shirley, M.[2023]

Glofitamab, a bispecific antibody, demonstrated a 53.8% overall response rate in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, with a complete response rate of 36.8%, indicating its efficacy in a heavily pretreated population.

The treatment had a manageable safety profile, with cytokine release syndrome occurring in 50.3% of patients but mostly at lower grades, and only 2.9% of patients withdrew due to adverse events, suggesting that glofitamab can be safely administered with prior obinutuzumab pretreatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. Hutchings, M., Morschhauser, F., Iacoboni, G., et al.[2023]

In a phase 2 study involving 155 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), glofitamab treatment resulted in a complete response in 39% of patients, demonstrating its efficacy as a therapy.

While glofitamab showed promising results, 62% of patients experienced adverse events of grade 3 or higher, with cytokine release syndrome being the most common, affecting 63% of participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Dickinson, MJ., Carlo-Stella, C., Morschhauser, F., et al.[2023]

In a real-world study of 43 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) treated with glofitamab, the median overall survival was 8.8 months, indicating promising efficacy in a heavily pretreated population.

However, the study also highlighted significant safety concerns, with treatment-related deaths occurring due to cytokine release syndrome and febrile neutropenia, emphasizing the need for careful monitoring of hematological toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data. Birtas Atesoglu, E., Gulbas, Z., Uzay, A., et al.[2023]

Glofitamab is a promising new treatment for B cell lymphomas that do not respond to standard R-CHOP chemotherapy, which fails in over one-third of cases.

As a bispecific antibody targeting CD20 and CD3, glofitamab works by engaging T cells to attack tumor cells, offering a novel approach for patients with relapsed or refractory lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab therapy for diffuse large B cell lymphoma: latest updates from the 2022 ASH Annual Meeting. Wang, C., Liu, Y.[2023]

Glofitamab is a novel bispecific T-cell recruiting antibody that targets both CD20 on B-cells and CD3 on T-cells, showing over 50% complete response rates in heavily treated patients with aggressive and indolent B-cell lymphoma during Phase 1 trials.

The unique 2:1 configuration of glofitamab allows for an extended half-life and superior binding to CD20, making it a promising option for patients with limited treatment choices, with ongoing trials evaluating its efficacy in combination therapies and earlier treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab CD20-TCB bispecific antibody. Minson, A., Dickinson, M.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Glofitamab: First Approval. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Glofitamab therapy for diffuse large B cell lymphoma: latest updates from the 2022 ASH Annual Meeting. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Glofitamab CD20-TCB bispecific antibody. [2022]