Polatuzumab Vedotin + R-GDP for Diffuse Large B-Cell Lymphoma

Overseen By Leah Randolph

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Infections, Hearing loss, Pregnancy, Cardiac disease, 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: Unknown

Duration: 4 months

44 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that prior cancer treatment must be completed at least 14 days before starting the trial, so you might need to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Polatuzumab Vedotin in combination with R-GDP for treating Diffuse Large B-Cell Lymphoma?

Polatuzumab Vedotin, when combined with bendamustine and rituximab, has shown effectiveness in treating relapsed or refractory diffuse large B-cell lymphoma, with a complete response rate of 40% compared to 18% for bendamustine and rituximab alone. This suggests potential effectiveness when used with other combinations like R-GDP. ^{1 2 3 4 5}

Is the combination of Polatuzumab Vedotin with R-GDP safe for treating diffuse large B-cell lymphoma?

Polatuzumab Vedotin, when combined with other drugs like rituximab and bendamustine, has been shown to have a manageable safety profile in patients with diffuse large B-cell lymphoma. Common side effects include low blood cell counts and nerve damage, but these are generally manageable. ^{1 4 6 7 8}

What makes the drug Polatuzumab Vedotin + R-GDP unique for treating diffuse large B-cell lymphoma?

Polatuzumab Vedotin is unique because it is an antibody-drug conjugate that specifically targets the CD79b protein on B-cells, delivering a powerful toxin directly to the cancer cells. This drug is combined with R-GDP (rituximab, gemcitabine, dexamethasone, and cisplatin) to enhance its effectiveness, especially in patients who have relapsed or are resistant to other treatments. ^{1 4 5 9 10}

What is the purpose of this trial?

This study aimed to evaluate the efficacy of a novel regimen consisting of polatuzumab vedotin in combination with rituximab, gemcitabine, dexamethasone, and cisplatin (PV-RGDP) for the treatment of diffuse large B-cell lymphoma that either came back or did not improve after the treatments (rrDLBCL). This combination has not been approved by the Food and Drug Administration (FDA) for the treatment of rrDLBCL. Salvage therapy (treatment after standard treatment failed) needs to be improved. Rituximab, gemcitabine, dexamethasone, and cisplatin combination is a standard therapy for rrDLBCL and polatuzumab vedotin (PV) is a novel antibody-drug conjugate targeting CD79b. PV has shown efficacy in the setting of rrDLBCL and can improve the response rates of standard salvage therapy. This study will focus on subjects in the first relapse (one prior regimen) and will include both subjects who are transplant eligible and those who are transplant ineligible.

Research Team

Christopher E. Dittus

Principal Investigator

Division of Hematology | Lymphoma Program Lineberger Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with diffuse large B-cell lymphoma that has returned after one prior treatment. They can be eligible or ineligible for a stem cell transplant, must have an ECOG Performance Status of 0-2, and show active disease on scans. Exclusions include severe allergies to monoclonal antibodies, significant heart or lung issues, hearing loss affecting daily life, pregnancy/breastfeeding intentions within a year post-treatment, and previous polatuzumab vedotin exposure.

Inclusion Criteria

Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information

I can take care of myself and am up and about more than half of my waking hours.

I finished my last cancer treatment at least 14 days ago and have recovered from its side effects.

Exclusion Criteria

I do not have any severe infections that could increase my risk during the study.

History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine

I have been treated with polatuzumab vedotin before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the PV-RGDP chemotherapy regimen for relapsed or refractory diffuse large B-cell lymphoma

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Cisplatin
• Dexamethasone
• Gemcitabine
• Polatuzumab Vedotin (PV)
• Rituximab

Trial Overview The study tests the effectiveness of adding polatuzumab vedotin (PV) to the standard rrDLBCL salvage therapy regimen (rituximab-gemcitabine-dexamethasone-cisplatin). PV-RGDP aims to improve response rates in patients whose cancer returned after initial treatment. The combination isn't FDA-approved yet; this trial will assess its efficacy.

Participant Groups

Group I: Single Arm Experimental Treatment 7 Interventions

The subjects with diffuse large B-cell lymphoma were relapsed or refractory after the first treatment and receiving the study protocol treatment.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

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

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 phase 3 trial involving 879 patients with untreated intermediate-risk or high-risk diffuse large B-cell lymphoma (DLBCL), the modified regimen pola-R-CHP (which replaces vincristine with polatuzumab vedotin) showed a significantly higher progression-free survival rate at 2 years (76.7%) compared to the standard R-CHOP regimen (70.2%).

The overall survival rates at 2 years were similar between the pola-R-CHP and R-CHOP groups (88.7% vs. 88.6%), indicating that while pola-R-CHP may reduce the risk of disease progression, it does not significantly improve overall survival compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. Tilly, H., Morschhauser, F., Sehn, LH., et al.[2022]

Polatuzumab vedotin, when combined with bendamustine and rituximab (polatuzumab-BR), is an effective treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), offering a new therapeutic avenue for those who do not respond to standard treatments.

This combination therapy is considered safe and is particularly beneficial for transplant-ineligible patients, with ongoing trials exploring its use alongside other treatments like CAR-T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of polatuzumab vedotin for the treatment of patients with diffuse large B-cell lymphoma. Walji, M., Assouline, S.[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, is effective for treating relapsed/refractory diffuse large B-cell lymphoma when combined with bendamustine and rituximab.

Research by Kawasaki et al. suggests potential mechanisms of resistance to polatuzumab vedotin in lymphoma cells, which could inform future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

United we stand: Double targeting of CD79B and CD20 in diffuse large B-cell lymphoma. Tarantelli, C., Bertoni, F.[2023]

In a study of 71 patients with relapsed/refractory diffuse large B-cell lymphoma, the combination of polatuzumab vedotin with bendamustine and rituximab (Pola-BR) showed an overall response rate of 47.9%, with a complete response rate of 32.4% after a median of 3 treatment cycles.

The treatment demonstrated a manageable safety profile, with the most common severe side effects being grade 3-4 neutropenia and thrombocytopenia, indicating that Pola-BR is a promising and effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin, rituximab, and bendamustine combination in relapsed or refractory diffuse large B-cell lymphoma: a real-world data from Turkey. Dal, MS., Ulu, BU., Uzay, A., et al.[2023]

The recommended phase II dose (RP2D) of pinatuzumab vedotin for treating relapsed/refractory non-Hodgkin lymphoma was established at 2.4 mg/kg, which was well tolerated with manageable side effects, primarily neutropenia and peripheral neuropathy.

At the RP2D, pinatuzumab vedotin showed promising antitumor activity, with objective responses in 36% of patients with diffuse large B-cell lymphoma and 50% of patients with indolent non-Hodgkin lymphoma, while no responses were observed in chronic lymphocytic leukemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of the Anti-CD22 Antibody-Drug Conjugate Pinatuzumab Vedotin with/without Rituximab in Patients with Relapsed/Refractory B-cell Non-Hodgkin Lymphoma. Advani, RH., Lebovic, D., Chen, A., et al.[2018]

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]

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 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]

References

1. 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]

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

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. [2022]

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

An evaluation of polatuzumab vedotin for the treatment of patients with diffuse large B-cell lymphoma. [2021]

4. 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]

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

United we stand: Double targeting of CD79B and CD20 in diffuse large B-cell lymphoma. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin, rituximab, and bendamustine combination in relapsed or refractory diffuse large B-cell lymphoma: a real-world data from Turkey. [2023]

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

Phase I Study of the Anti-CD22 Antibody-Drug Conjugate Pinatuzumab Vedotin with/without Rituximab in Patients with Relapsed/Refractory B-cell Non-Hodgkin Lymphoma. [2018]

8. 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]

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

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

10. 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]