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

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

41 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of drugs to treat high-risk diffuse large B-cell lymphoma in patients who have not been treated before. The drugs help the immune system attack cancer and directly kill cancer cells. The standard treatment for diffuse large B-cell lymphoma (DLBCL) includes rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

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.

What data supports the effectiveness of the drug combination Glofitamab + Polatuzumab-R-CHP for treating Diffuse Large B-Cell Lymphoma?

Research shows that polatuzumab vedotin, part of the treatment, has demonstrated significant clinical efficacy in relapsed or refractory diffuse large B-cell lymphoma, leading to its FDA approval in combination with other drugs. Additionally, glofitamab, another component, has been studied for its survival outcomes in similar conditions, although it did not show a clear advantage over other treatments. ^{1 2 3 4 5}

Is the combination of Glofitamab and Polatuzumab-R-CHP safe for humans?

Polatuzumab vedotin, when used in combination with other drugs for treating diffuse large B-cell lymphoma, has shown an acceptable safety profile in clinical trials. Common side effects include blood-related issues like anemia (low red blood cell count) and neutropenia (low white blood cell count), but no fatal adverse events were observed. ^{1 3 6 7 8}

What makes the drug combination of Glofitamab, Polatuzumab, and R-CHP unique for treating diffuse large B-cell lymphoma?

This drug combination is unique because it includes polatuzumab vedotin, an antibody-drug conjugate that targets CD79b on B-cells and delivers a toxin to kill cancer cells, and is combined with glofitamab, a novel bispecific antibody, and R-CHP chemotherapy, offering a new approach for patients with relapsed or refractory diffuse large B-cell lymphoma who have limited treatment options. ^{1 2 3 7 9}

Research Team

Jennifer Crombie, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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.

Women of childbearing potential must use effective contraception

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

References

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

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

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin: Current Role and Future Applications in the Treatment of Patients with Diffuse Large B-Cell Lymphoma. [2021]

4. United States 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. [2023]

5. 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]

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

Polatuzumab Vedotin: First Global Approval. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. [2022]

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

A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B-cell lymphoma. [2021]

9. 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]