Glofitamab + Pola-R-CHP for B-Cell Lymphoma

Recruiting at 334 trial locations

Overseen By Reference Study ID Number: GO44145 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants, Monoclonal antibodies

Disqualifiers: Organ transplant, Indolent lymphoma, CNS disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

1130 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the efficacy and safety of glofitamab in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs Pola-R-CHP in participants with previously untreated CD20-positive large B-cell lymphoma (LBCL).

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking systemic immunosuppressive agents at least 4 weeks before starting the study treatment. If you are on corticosteroids, you must not exceed 30 mg/day of prednisone or equivalent for purposes other than lymphoma symptom control. Other medications are not specifically mentioned, so please consult with the trial team for guidance on your specific medications.

What data supports the effectiveness of the drug combination Glofitamab + Pola-R-CHP for B-Cell Lymphoma?

Polatuzumab vedotin, part of the combination, has shown effectiveness in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) when combined with other drugs, achieving a higher complete response rate compared to standard treatments. Glofitamab has been approved in Canada for relapsed or refractory DLBCL, indicating its potential effectiveness in similar conditions. ^{1 2 3 4 5}

Is the combination of Glofitamab and Pola-R-CHP safe for treating B-cell lymphoma?

The combination of Polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) has shown similar safety to the standard R-CHOP treatment in patients with diffuse large B-cell lymphoma, with comparable rates of serious side effects and treatment discontinuation. Glofitamab, approved for certain types of B-cell lymphoma, is still being studied for safety in combination with other treatments. ^{1 2 6 7 8}

What makes the drug combination of Glofitamab, Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone unique for treating B-cell lymphoma?

This drug combination is unique because it includes Glofitamab, a bispecific antibody that engages T-cells to target cancer cells, and Polatuzumab vedotin, an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, offering a novel approach for patients who have limited treatment options or are ineligible for CAR T-cell therapy. ^{2 4 5 8 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for people who haven't been treated for CD20-positive large B-cell lymphoma. They should be relatively active and healthy (ECOG score 0-2), have a measurable tumor, normal heart function (LVEF ≥50%), and good blood counts. Participants must test negative for COVID-19, HIV, and ensure their tumor tissue is available for the study.

Inclusion Criteria

I am able to care for myself and perform daily activities.

Your heart's pumping function is normal, as shown in a heart scan or ultrasound.

You have tested negative for HIV unless otherwise specified in the protocol.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Glofitamab in combination with Pola-R-CHP or Pola-R-CHP alone

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Glofitamab
• Polatuzumab vedotin
• Rituximab, Cyclophosphamide, Doxorubicin, Prednisone

Trial Overview The trial tests if Glofitamab combined with Pola-R-CHP is more effective than just Pola-R-CHP alone in treating large B-cell lymphoma. Patients will receive these treatments to see which one works better at fighting cancer.

Participant Groups

Group I: Glofitamab + Pola-R-CHP Experimental Treatment 6 Interventions

Participants will receive glofitamab in combination with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP).

Group II: Pola-R-CHP Active Control 5 Interventions

Participants will receive Pola-R-CHP.

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?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

In a study involving 85 patients with untreated diffuse large B-cell lymphoma, the combination of polatuzumab vedotin with standard chemotherapy (R-CHP or G-CHP) showed promising preliminary efficacy, with 89% of patients achieving an overall response and 77% achieving a complete response.

The safety profile of polatuzumab vedotin was manageable, with common adverse events including neutropenia and peripheral neuropathy, leading to the establishment of a recommended phase 2 dose of 1.8 mg/kg for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Tilly, H., Morschhauser, F., Bartlett, NL., et al.[2023]

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]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has been approved for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in patients who are ineligible for transplant, showing a complete response rate of 40% compared to 18% for standard treatment with bendamustine and rituximab (BR).

The most common side effects associated with polatuzumab vedotin treatment include cytopenias (a reduction in blood cells) and peripheral neuropathy, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin to treat relapsed or refractory diffuse large B-cell lymphoma, in combination with bendamustine plus rituximab. Amaya, ML., Jimeno, A., Kamdar, M.[2021]

In a study of patients with transplantation-ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), the combination of polatuzumab vedotin with bendamustine and rituximab (pola-BR) resulted in a significantly higher complete response (CR) rate of 40% compared to 17.5% with bendamustine and rituximab alone, indicating improved efficacy.

Patients receiving pola-BR also experienced longer progression-free survival (9.5 months vs. 3.7 months) and overall survival (12.4 months vs. 4.7 months), although there were higher rates of certain side effects like neutropenia and peripheral neuropathy, which were mostly manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Sehn, LH., Herrera, AF., Flowers, CR., et al.[2021]

The study evaluated the antibody-drug conjugate polatuzumab vedotin (pola) combined with rituximab/obinutuzumab and chemotherapy in treating B-cell non-Hodgkin lymphoma, showing that pola's pharmacokinetics were consistent and dose-proportional across different treatment cycles.

There were no significant drug-drug interactions between pola and the chemotherapy regimen (R/G-CHP), indicating that pola can be safely used in combination with these treatments for previously untreated diffuse large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. Shemesh, CS., Agarwal, P., Lu, T., et al.[2020]

In the phase 3 POLARIX study, the combination of polatuzumab vedotin with rituximab and chemotherapy (Pola-R-CHP) significantly improved progression-free survival (PFS) in patients with untreated diffuse large B-cell lymphoma compared to the standard treatment R-CHOP, with a hazard ratio of 0.64 indicating a 36% reduction in the risk of disease progression.

The safety profile of Pola-R-CHP was comparable to R-CHOP, with similar rates of serious adverse events and peripheral neuropathy, suggesting that Pola-R-CHP is both effective and safe for patients in both the global and Asian populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in previously untreated DLBCL: an Asia subpopulation analysis from the phase 3 POLARIX trial. Song, Y., Tilly, H., Rai, S., et al.[2023]

Polatuzumab vedotin is an antibody-drug conjugate that targets CD79b on B cells, delivering a cytotoxic agent (MMAE) to inhibit cell division and induce cell death, making it a promising treatment for certain blood cancers.

In June 2019, polatuzumab vedotin received accelerated FDA approval for use with bendamustine and rituximab in adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), and it is currently under review in the EU and in various stages of development for other related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin: First Global Approval. Deeks, ED.[2023]

In a phase 2 study involving 123 patients with relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma, both antibody-drug conjugates, R-pola and R-pina, showed promising efficacy, with R-pina achieving a higher objective response rate in diffuse large B-cell lymphoma (60%) compared to R-pola (54%).

R-pola demonstrated a more favorable safety profile, with fewer severe adverse events (grade 3-5) compared to R-pina, leading to its selection for further development due to longer durations of response and a better overall benefit-risk ratio.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Morschhauser, F., Flinn, IW., Advani, R., et al.[2019]

In a study of 61 Greek patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), the combination of polatuzumab vedotin and bendamustine-rituximab (Pola-BR) showed a response rate of 43%, with 25% achieving complete remission and 18% partial remission.

The treatment demonstrated an acceptable safety profile, with 55% of patients experiencing grade ≥3 adverse events, primarily hematologic, suggesting that Pola-BR could serve as an effective bridging therapy before further treatments like CAR-T cell therapy or stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-life experience with the combination of polatuzumab vedotin, rituximab, and bendamustine in aggressive B-cell lymphomas. Dimou, M., Papageorgiou, SG., Stavroyianni, N., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. [2023]

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

Glofitamab: First Approval. [2023]

3. Spain pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin to treat relapsed or refractory diffuse large B-cell lymphoma, in combination with bendamustine plus rituximab. [2021]

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

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. [2020]

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

Polatuzumab vedotin in previously untreated DLBCL: an Asia subpopulation analysis from the phase 3 POLARIX trial. [2023]

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

Polatuzumab Vedotin: First Global Approval. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). [2019]

9. England pubmed.ncbi.nlm.nih.gov

Real-life experience with the combination of polatuzumab vedotin, rituximab, and bendamustine in aggressive B-cell lymphomas. [2021]