Polatuzumab Vedotin + R-CHP vs R-CHOP for Diffuse Large B-Cell Lymphoma

(POLARIX Trial)

Recruiting at 324 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Corticosteroids, Cytotoxic drugs, Monoclonal antibodies

Disqualifiers: Organ transplant, Peripheral neuropathy, Indolent lymphoma, CNS lymphoma, others

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: 8

Duration: 24 weeks

1000 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using corticosteroids at more than 30 mg/day of prednisone or equivalent for reasons other than lymphoma symptom control, you may need to adjust this. Also, if you have used any monoclonal antibodies recently, you might need to wait before starting the trial.

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

Research shows that Polatuzumab Vedotin combined with R-CHP significantly improves progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) compared to the standard R-CHOP treatment in patients with Diffuse Large B-Cell Lymphoma. This means patients on Polatuzumab Vedotin + R-CHP tend to have a longer period without the disease progressing. ^{1 2 3 4 5}

Is Polatuzumab Vedotin + R-CHP safe for humans?

In a study comparing Polatuzumab Vedotin combined with R-CHP to the standard R-CHOP treatment for diffuse large B-cell lymphoma, the safety was found to be similar between the two groups. Both treatments had comparable rates of serious side effects, including severe adverse events and peripheral neuropathy (nerve damage). ^{1 2 3 6 7}

How is the drug Polatuzumab Vedotin + R-CHP different from other treatments for diffuse large B-cell lymphoma?

Polatuzumab Vedotin + R-CHP is unique because it includes polatuzumab vedotin, an antibody-drug conjugate that targets CD79b on B cells, and has shown improved progression-free survival compared to the standard R-CHOP regimen, especially in certain subtypes of the disease. ^{1 2 3 4 8}

What is the purpose of this trial?

This Phase III, randomized, double-blind, placebo-controlled study will compare the efficacy, safety, and pharmacokinetics of polatuzumab vedotin plus R-CHP versus R-CHOP in participants with previously untreated diffuse large B-cell lymphoma (DLBCL).

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with previously untreated CD20-positive diffuse large B-cell lymphoma. Participants must have a life expectancy of at least 12 months, good heart function (LVEF ≥50%), and an ECOG Performance Status of 0-2. They should agree to use contraception and not donate sperm or eggs. Exclusions include prior organ transplants, certain other lymphomas, CNS involvement, recent live vaccines, significant ECG abnormalities, major surgery within the last month, HIV or hepatitis infection among others.

Inclusion Criteria

International Prognostic Index (IPI) score of 2-5

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

My heart pumps well, with an ejection fraction of 50% or more.

Exclusion Criteria

I have had treatment for DLBCL, but only a node biopsy.

I have not received any live vaccines in the last 28 days.

I do not have any active infections or significant infections in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive polatuzumab vedotin plus R-CHP or R-CHOP for 6 cycles, with additional rituximab monotherapy in Cycles 7 and 8

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Polatuzumab Vedotin
• Rituximab-Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP)
• Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP)

Trial Overview The study compares Polatuzumab Vedotin combined with R-CHP versus the standard R-CHOP therapy in treating diffuse large B-cell lymphoma. It's a Phase III trial where participants are randomly assigned to either treatment group in a double-blind manner; neither they nor the researchers know who receives which treatment until after the results are collected.

Participant Groups

Group I: R-CHP plus Vincristine Placebo plus Polatuzumab Vedotin Experimental Treatment 6 Interventions

Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) intravenously (IV), placebo for vincristine IV, rituximab 375 milligrams per square meter (mg/m\^2) IV, cyclophosphamide 750 mg/m\^2 IV, and doxorubicin 50 mg/m\^2 IV on Day 1 and prednisone 100 milligrams per day (mg/day) orally (PO) on Days 1-5 of every 21-day cycle for 6 cycles. Rituximab 375 mg/m\^2 IV will be administered as monotherapy in Cycles 7 and 8.

Group II: R-CHOP plus Polatuzumab Vedotin Placebo Placebo Group 6 Interventions

Participants will receive placebo for polatuzumab vedotin, rituximab 375 mg/m\^2 IV, cyclophosphamide 750 mg/m\^2 IV, doxorubicin 50 mg/m\^2 IV, and vincristine 1.4 mg/m\^2 IV (maximum 2 milligrams per dose \[mg/dose\]) on Day 1 and prednisone 100 mg/day PO on Days 1-5 of every 21-day cycle for 6 cycles. Rituximab 375 mg/m\^2 IV will be administered as monotherapy in Cycles 7 and 8.

Polatuzumab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Polivy for:

• Diffuse large B-cell lymphoma (DLBCL)
• High-grade B-cell lymphoma (HGBL)

Approved in European Union as Polivy for:

• Diffuse large B-cell lymphoma (DLBCL)
• High-grade B-cell lymphoma (HGBL)

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 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]

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 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]

In a study of 69 patients with aggressive B-cell lymphoma treated with polatuzumab vedotin combined with bendamustine and rituximab, a 50% response rate was observed, with a 24% complete response rate, indicating some efficacy in a real-world setting.

However, the median progression-free survival (PFS) was only 2.0 months, and survival was 5.3 months, which is lower than what was reported in clinical trials, particularly for patients with prior refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin for Relapsed/Refractory Aggressive B-cell Lymphoma: A Multicenter Post-marketing Analysis. Smith, SD., Lopedote, P., Samara, Y., et al.[2022]

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, 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]

References

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

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

2. Germany pubmed.ncbi.nlm.nih.gov

Superiority of polatuzumab vedotin over other novel agents in previously untreated ABC-type diffuse large B-cell lymphoma: a network meta-analysis of 20 RCTs. [2023]

3. 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]

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

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

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

Comparison of statistical methods for extrapolating survival in previously untreated diffuse large B-cell lymphoma: results based on the POLARIX study. [2023]

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

Polatuzumab Vedotin for Relapsed/Refractory Aggressive B-cell Lymphoma: A Multicenter Post-marketing Analysis. [2022]

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

Polatuzumab Vedotin: First Global Approval. [2023]

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

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