Glofitamab + Polatuzumab-R-CHP for Diffuse Large B-Cell Lymphoma

Not currently recruiting at 3 trial locations

Overseen By Jennifer Crombie, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Philippe Armand, MD, PhD

Must not be taking: Monoclonal antibodies, Cytotoxic drugs

Disqualifiers: Organ transplant, Indolent lymphoma, 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

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for diffuse large B-cell lymphoma (DLBCL), a type of blood cancer. Researchers are evaluating the effectiveness of Glofitamab (a type of immunotherapy) and Polatuzumab (an antibody-drug conjugate) in combination with a standard chemotherapy regimen called R-CHP for treating this high-risk condition. Individuals who have not yet received treatment for DLBCL and have CD20-positive DLBCL may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that prior use of certain treatments, like monoclonal antibodies or cytotoxic drugs, may affect eligibility. It's best to discuss your current medications with the trial team to get a clear answer.

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

Studies have shown that the combination of Glofitamab, Polatuzumab, and the R-CHP chemotherapy regimen is generally well-tolerated in patients with diffuse large B-cell lymphoma. Research indicates that most patients experienced manageable side effects. For instance, cytokine release syndrome (CRS) occurred in 21% of patients, and these cases were mild to moderate, indicating non-severe side effects.

Moreover, patients received more than 94% of the planned doses, demonstrating their ability to handle the treatment well. While monitoring for side effects remains important, existing data suggest that this combination treatment is safe for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Glofitamab, Polatuzumab, and R-CHP for treating Diffuse Large B-Cell Lymphoma because it offers a novel approach compared to the current standard treatments like R-CHOP. Glofitamab is a bispecific antibody that uniquely targets both CD20 and CD3, harnessing the immune system to directly attack cancer cells, which is different from traditional chemotherapy. Polatuzumab vedotin, an antibody-drug conjugate, targets CD79b on B-cells and delivers a potent toxin directly to the cancerous cells, reducing damage to healthy cells. This combination aims to enhance the effectiveness and specificity of treatment, potentially increasing remission rates and reducing side effects.

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

Research shows that Glofitamab and Polatuzumab may effectively treat diffuse large B-cell lymphoma (DLBCL). In this trial, participants will receive a combination of Glofitamab, Polatuzumab, and R-CHP chemotherapy. Glofitamab, an antibody, targets and treats DLBCL that has returned or is unresponsive to other treatments, with studies showing positive patient outcomes. Polatuzumab, another antibody, delivers a drug directly to cancer cells and has significantly improved the time patients live without disease progression in untreated DLBCL. Together, Glofitamab and Polatuzumab have demonstrated high success rates, indicating they work well in tandem. This combination, along with R-CHP chemotherapy, could be a strong option for treating high-risk DLBCL. ^{6 7 8 9 10}

Who Is on the Research Team?

Jennifer Crombie, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with untreated high-risk diffuse large B-cell lymphoma (DLBCL), a type of cancer. They must have an IPI score of 2-5, be in decent physical shape (ECOG 0-1-2), and their heart and other organs must work well. Women who can have babies and men must agree to use birth control. People with prior organ transplants, recent cancer treatments, or certain infections like HIV can't join.

Inclusion Criteria

I have a lymphoma lesion that shows up on scans.

I have chronic hepatitis B with no detectable virus in my blood.

I will not have unprotected sex or donate sperm during the trial.

Exclusion Criteria

I have tested positive for HIV or HTLV-1.

I am not allergic to the drugs used in this study.

I have not had an active infection or a flare-up of a hidden infection in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two cycles of polatuzumab-R-CHP and four cycles of glofitamab-polatuzumab-R-CHP, followed by two additional cycles of glofitamab alone

24 weeks

8 cycles of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Glofitamab
• Polatuzumab
• R-CHP

Trial Overview

The study tests Glofitamab combined with Polatuzumab alongside standard chemo R-CHP (Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Prednisone) for treating DLBCL. Glofitamab is a T-cell bispecific antibody; Polatuzumab is an antibody-drug conjugate; R-CHP are established chemotherapy drugs.

How Is the Trial Designed?

Group I: Polatuzumab + Glofitamab + R-CH Experimental Treatment 6 Interventions

-Participants will receive treatment interventions as outlined: Experimental: Safety Lead-In Phase of 6 Participants, Total Enrollment of 40 Participants * Polatuzumab, once, predetermined day and dosage per cycle, per protocol Cycles 1 - 6 * R-CHP (Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Prednisone * Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride once, predetermined day and dosage per cycle, per protocol Cycles 1 - 6: * Prednisone) 5 days, predetermined day and dosage per cycle, per protocol Cycles 1 - 6: * Glofitamab * twice, predetermined day and dosage per cycle, per protocol Cycle 3-6 * once, predetermined day and dosage per cycle, per protocol Cycle 7-8 * Participants who need urgent therapy are also allowed to proceed with one cycle of R-CHOP for 1 cycle per standard of care. * Participants will be followed for up to 5 years post-treatment.

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?

Philippe Armand, MD, PhD

Lead Sponsor

Trials

1

Recruited

40+

Jennifer Crombie, MD

Lead Sponsor

Trials

2

Recruited

80+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

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 has shown significant clinical activity and an acceptable safety profile in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), particularly when combined with anti-CD20 monoclonal antibodies and chemotherapy.

The recent POLARIX trial suggests that polatuzumab may also be effective in frontline treatment for DLBCL, potentially changing its role in managing patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. Varma, G., Wang, J., Diefenbach, C.[2022]

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]

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]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has shown significant clinical efficacy in treating relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and received accelerated FDA approval for use in patients who have failed at least two prior therapies.

The drug is currently being evaluated in combination with other therapies for previously untreated DLBCL patients, indicating its potential to play a broader role in the treatment of this heterogeneous disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin: Current Role and Future Applications in the Treatment of Patients with Diffuse Large B-Cell Lymphoma. Assi, R., Masri, N., Dalle, IA., et al.[2021]

In a study analyzing overall survival (OS) for five treatments of relapsed-refractory diffuse large B-cell lymphoma (DLBCL), tafasitamab plus lenalidomide showed the best OS with a median of 26.5 months and a hazard ratio of 0.514 compared to glofitamab, indicating it may be a more effective option.

Despite glofitamab's advanced mechanism as a bispecific antibody, it did not demonstrate a significant OS advantage over the other treatments, with a median survival of 11.7 months, suggesting that other therapies may be more beneficial for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatments for Relapsed-Refractory Diffuse Large B-cell Lymphoma: A Preliminary Evaluation of the Place in Therapy of Glofitamab, a Bispecific Monoclonal Antibody. Messori, A., Rivano, M., Mengato, D., et al.[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]

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]

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