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

(POLARIX Trial)

Not currently recruiting at 377 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for people with diffuse large B-cell lymphoma (DLBCL), a type of blood cancer. Researchers aim to determine if adding polatuzumab vedotin (Polivy) to the standard R-CHP treatment is more effective than the usual R-CHOP treatment. The trial compares the effectiveness, safety, and how the body processes these medicines. People who have never been treated for DLBCL and have a specific type of this cancer are suitable candidates for the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that the combination of polatuzumab vedotin and R-CHP is generally well-tolerated by people with diffuse large B-cell lymphoma (DLBCL). In earlier studies, patients who received this treatment experienced common side effects, such as low blood cell counts and nausea. However, these side effects were manageable, allowing most patients to continue their treatment.

The safety of polatuzumab vedotin plus R-CHP has undergone thorough study. It is approved as a first-choice treatment for DLBCL, indicating its safety for many patients.

Overall, while side effects exist, research suggests that the treatment is generally safe and tolerable. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for diffuse large B-cell lymphoma?

Most treatments for diffuse large B-cell lymphoma (DLBCL), like the standard R-CHOP regimen, involve a combination of chemotherapy drugs targeting cancer cells. But the experimental treatment featuring polatuzumab vedotin works differently, as it combines a targeted therapy approach. Polatuzumab vedotin is an antibody-drug conjugate that specifically targets and delivers a potent chemotherapy agent directly into the cancer cells, potentially increasing efficacy while reducing side effects. Researchers are excited because this targeted approach could improve outcomes for patients with DLBCL by offering a more precise attack on cancer cells compared to the broader effects of traditional chemotherapy.

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

Research shows that Polatuzumab Vedotin, combined with R-CHP, holds promise for treating diffuse large B-cell lymphoma (DLBCL). In early studies, all patients who received this combination experienced a complete response, with their cancer signs disappearing. It also rapidly reduced cancer cells. In this trial, one group of participants will receive Polatuzumab Vedotin with R-CHP, while another group will receive R-CHOP with a placebo for Polatuzumab Vedotin. These findings suggest that Polatuzumab Vedotin with R-CHP could be an effective treatment option for DLBCL. ^{6 7 8 9 10}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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, 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38813707/

new standards for diffuse large B-cell lymphoma? - PubMed Remarkable improvements in terms of complete response rate and overall survival have also been achieved with polatuzumab vedotin by combining ...

2. haematologica.org haematologica.org/article/view/haematol.2022.282362

new standards for diffuse large B-cell lymphoma? A recent update, including the first 12 patients treated with this regimen, demonstrated an overall response rate of 100% and rapid remission ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10589404/

Advances in Polatuzumab Vedotin-PIIQ Therapy Polatuzumab vedotin-piiq emerges as a promising therapeutic avenue for the management of diffuse B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00992

Efficacy and Safety of Glofitamab Plus Polatuzumab ... The primary results demonstrated high and durable responses, particularly for patients with primary refractory disease (CR rate, 52.5%) and ...

5. journals.lww.com journals.lww.com/hemasphere/fulltext/2022/12000/real_world_outcomes_of_relapsed_refractory_diffuse.3.aspx

Real-world Outcomes of Relapsed/Refractory Diffuse Large... The final overall response rate was 32.7% (18.2% complete response rate), with a best response rate of 49.1%. Median disease-free survival was reached at 12 ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7061

Efficacy and safety of polatuzumab vedotin plus rituximab ... Background: In the POLARIX study, Pola-R-CHP showed significant improvement in progression free survival (PFS) in previously untreated DLBCL ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39641321/

Efficacy and Safety of Polatuzumab Vedotin Plus Rituximab ... Polatuzumab vedotin plus R-CHP (Pola-R-CHP) is approved as a new standard first-line therapy for diffuse large B-cell lymphoma (DLBCL) based on the POLARIX ...

8. link.springer.com link.springer.com/article/10.1007/s00277-025-06619-0

Polatuzumab vedotin, rituximab, cyclophosphamide, ... Polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) therapy in diffuse large B-cell lymphoma in patients ...

9. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7767/528782/Polatuzumab-Vedotin-Rituximab-Cyclophosphamide

Polatuzumab Vedotin, Rituximab, Cyclophosphamide ... Background: The POLARIX trial demonstrated that Pola-R-CHP provided superior disease control than R-CHOP in previously untreated DLBCL with ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT03274492

NCT03274492 | A Study Comparing the Efficacy and ... This Phase III, randomized, double-blind, placebo-controlled study will compare the efficacy, safety, and pharmacokinetics of polatuzumab vedotin plus R-CHP ...