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

Recruiting at 360 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with CD20-positive large B-cell lymphoma, a type of blood cancer. Researchers are testing whether adding glofitamab, a potential new drug, to the standard cancer treatment regimen (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) proves more effective and safe than the standard regimen alone. Individuals who have not yet received treatment for this specific type of lymphoma might be suitable candidates. The goal is to determine if this new combination can more effectively combat the disease. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining glofitamab with polatuzumab vedotin and other chemotherapy drugs is generally well-tolerated by patients with large B-cell lymphoma. This combination, known as Glofit-Pola, has proven effective and safe for patients who have undergone multiple treatments. Most reported side effects were mild to moderate, indicating they were not too serious.

Polatuzumab vedotin is already approved for use with other drugs for certain types of lymphoma, so doctors are familiar with its side effects.

Overall, this treatment is in a late stage of research, meaning it has been tested in humans for safety. This suggests it is considered safe enough for more people to try. However, discussing any potential risks with a healthcare provider before joining the trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for B-cell lymphoma?

Researchers are excited about combining glofitamab with Pola-R-CHP for B-cell lymphoma because it brings a fresh approach to targeting the cancer. Unlike standard treatments like R-CHOP, which mainly involve chemotherapy and rituximab, glofitamab is a bispecific antibody that can simultaneously bind to two different targets: one on the cancer cells and one on immune cells. This dual-targeting mechanism helps the immune system recognize and attack the lymphoma cells more effectively. Adding glofitamab to the regimen could enhance the immune response, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for B-cell lymphoma?

This trial will compare two treatment approaches for B-cell lymphoma. One group of participants will receive Glofitamab combined with Pola-R-CHP, which includes polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone. Studies have shown that using glofitamab with polatuzumab vedotin and other drugs results in high success rates and long-lasting improvements for patients with large B-cell lymphoma. Research indicates this combination works well for patients who have tried other treatments without success. Glofitamab is an antibody that helps the immune system find and attack cancer cells, while polatuzumab vedotin delivers a toxic substance directly to the cancer cells. Together, these drugs have shown promising results in treating this type of lymphoma. The treatment is effective and generally safe to manage. Another group in this trial will receive Pola-R-CHP alone as an active comparator. ^{3 5 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41115257/

Efficacy and Safety of Glofitamab Plus Polatuzumab ... Conclusion: Glofit-Pola demonstrated high efficacy and durable responses, with manageable safety, in heavily pretreated patients with R/R LBCL, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04231877

Study Details | NCT04231877 | Polatuzumab Vedotin and ... Giving polatuzumab vedotin in combination chemotherapy with or without glofitamab may help treat patients with aggressive large B-cell lymphoma. Detailed ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8728095/

Novel biologic therapies in relapsed or refractory diffuse ... Patients with diffuse large B-cell lymphoma who have refractory or relapsed disease following first line treatment have a poor prognosis when treated with ...

4. cancernetwork.com cancernetwork.com/view/glofitamab-polatuzumab-vedotin-exhibits-response-durability-in-r-r-lbcl

Glofitamab/Polatuzumab Vedotin Exhibits Response ... “[Glofitamab/polatuzumab vedotin] demonstrated high efficacy, with frequent and durable responses in patients with heavily pretreated [relapsed/ ...

5. onclive.com onclive.com/view/glofitamab-based-combo-confers-high-response-rates-in-heavily-pretreated-relapsed-refractory-lbcl

Glofitamab-Based Combo Confers High Response Rates ... Glofitamab and polatuzumab vedotin demonstrate high response rates and durable remissions in relapsed/refractory large B-cell lymphoma, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06047080

NCT06047080 | An Open-Label Study Comparing ... The purpose of this study is to compare the efficacy and safety of glofitamab in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, ...

7. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/non-hodgkins-lymphoma/an-open-label-study-comparing-glofitamab-and-polatuzuma-51322.html

A clinical trial to compare glofitamab plus Pola-R-CHP wi... Pola-R-CHP is a standard first treatment that combines polatuzumab vedotin (pola) plus rituximab (R), cyclophosphamide (C), doxorubicin (H), and prednisone (P).

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-02086

An Open-Label Study Comparing Glofitamab and ... The purpose of this study is to compare the efficacy and safety of glofitamab in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, ...