Polatuzumab Vedotin Combo for Lymphoma

(POLARGO Trial)

No longer recruiting at 133 trial locations

Overseen By MO40598 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Immunotherapy, Immunosuppressive therapy

Disqualifiers: Severe allergies, CNS lymphoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for diffuse large B-cell lymphoma (DLBCL) that has returned or not responded to previous treatments. The study evaluates the effectiveness of adding the drug polatuzumab vedotin (Polivy) to the standard regimen of rituximab, gemcitabine, and oxaliplatin. It consists of two stages: first, assessing safety, and then comparing the new combination to the standard treatment. Candidates may qualify if they have recurrent DLBCL and have tried at least one other treatment. As a Phase 3 trial, this study is the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you've had recent chemotherapy, immunotherapy, or immunosuppressive therapy within 2 weeks before starting the trial.

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

Research has shown that combining polatuzumab vedotin with rituximab, gemcitabine, and oxaliplatin (Pola-R-GemOx) is generally safe for patients. In a recent study, participants tolerated this treatment mix well. Some experienced peripheral neuropathy, which causes numbness and tingling, but adjusting the dose managed these symptoms, and no severe cases occurred. These findings suggest that the treatment should be safe for most people, although, like any medical treatment, it may have some side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Polatuzumab Vedotin combo for lymphoma because it introduces a novel approach by incorporating polatuzumab vedotin, an antibody-drug conjugate that specifically targets and destroys cancer cells. Unlike traditional treatments that might not differentiate between healthy and cancerous cells, this targeted therapy reduces damage to normal cells, potentially leading to fewer side effects. Additionally, combining polatuzumab vedotin with established drugs like rituximab, gemcitabine, and oxaliplatin could enhance treatment efficacy, offering hope for improved outcomes in patients with lymphoma.

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

Research has shown that the Pola-R-GemOx treatment combination, which participants in this trial may receive, significantly benefits people with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL). One study found that those who received Pola-R-GemOx lived for a median of 19.5 months, compared to 12.5 months for those on the standard R-GemOx treatment, another treatment arm in this trial. The response rate nearly doubled, increasing from 24.6% with the standard treatment to 52.7% with the addition of polatuzumab vedotin. These findings suggest that this combination is more effective than the standard treatment. ^{1 2 3 6 7}

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 relapsed or refractory diffuse large B-cell lymphoma who have had at least one prior therapy. They should not be planning a stem cell transplant, must agree to use contraception if of childbearing potential, and cannot have severe allergies to monoclonal antibodies or certain chemotherapy drugs.

Inclusion Criteria

My blood counts are within a healthy range.

I agree to not have sex or use birth control and not donate sperm.

I have had treatment for transformed lymphoma or received anthracycline for indolent lymphoma.

Exclusion Criteria

History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products

I have not received a live vaccine in the last 4 weeks.

I haven't had major surgery in the last 6 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Safety of polatuzumab vedotin plus rituximab, gemcitabine, and oxaliplatin is assessed in 10 participants

Up to 8 cycles (21 days per cycle)

Randomized Controlled Trial (RCT)

Comparison of Pola-R-GemOx versus R-GemOx alone using overall survival as the primary endpoint

Up to 8 cycles (21 days per cycle)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 49 months

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Oxaliplatin
• Polatuzumab Vedotin
• Rituximab

Trial Overview The study tests the safety and effectiveness of Polatuzumab Vedotin combined with Rituximab, Gemcitabine, and Oxaliplatin (R-GemOx) against R-GemOx alone in patients whose lymphoma has returned after treatment or did not respond well to previous therapies.

How Is the Trial Designed?

Group I: Pola-R-GemOx (Stage 2) Experimental Treatment 4 Interventions

Participants will receive polatuzumab vedotin 1.8 mg/kg for a maximum dose of 240 mg/cycle administered IV and rituximab 375 mg/m\^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m\^2 administered IV and oxaliplatin 100 mg/m\^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.

Group II: Pola-R-GemOx (Stage 1) Experimental Treatment 4 Interventions

Participants will receive polatuzumab vedotin 1.8 milligrams per kilogram (mg/kg) for a maximum dose of 240 mg per cycle (mg/cycle) administered intravenously (IV) and rituximab 375 milligrams per square meter (mg/m\^2) administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m\^2 administered IV and oxaliplatin 100 mg/m\^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.

Group III: R-GemOx (Stage 2) Active Control 3 Interventions

Participants will receive rituximab 375 mg/m\^2 administered IV on Day 1. Participants will receive gemcitabine 1000 mg/m\^2 administered IV and oxaliplatin 100 mg/m\^2 administered IV on Day 2. Each cycle will consist of 21 days with up to 8 cycles of treatment administration.

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

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

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

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9430639/

POLATUZUMAB VEDOTIN PLUS RITUXIMAB, ... In the safety run-in stage, Pola-R-GemOx was safe and tolerable. PN was manageable with dose interruptions and reductions; no cases of grade ≥3 PN were ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04182204

NCT04182204 | A Study to Evaluate the Safety and ... The safety run-in stage (Stage 1) will assess the safety of polatuzumab vedotin plus rituximab, gemcitabine and oxaliplatin (Pola-R-GemOx) in 10 participants.

3. library.ehaweb.org library.ehaweb.org/eha/2025/eha2025-congress/4159178/matthew.matasar.polatuzumab.vedotin.rituximab.gemcitabine.and.oxaliplatin.html

POLATUZUMAB VEDOTIN, RITUXIMAB, GEMCITABINE ... Median OS was 19.5 months (95% CI: 13.3-not evaluable) for Pola-R-GemOx vs 12.5 months (95% CI: 8.9-15.8) for R-GemOx. OS benefit was consistent ...

4. ascopost.com ascopost.com/issues/july-25-2025/phase-iii-polargo-addition-of-polatuzumab-vedotin-improves-overall-survival-in-refractory-dlbcl/

Polatuzumab Vedotin–Based Regimen Improves Overall ... Polatuzumab vedotin plus R-GemOx also nearly doubled the response rate, from 24.6% with standard therapy to 52.7%; thecomplete response rate was ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07001540

Study Details | NCT07001540 | Evaluation of the Efficacy ... This is a prospective, multicenter, single-arm clinical study designed to evaluate the efficacy and safety of Polatuzumab Vedotin combined with Rituximab, ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-00869

A Study to Evaluate the Safety and Efficacy of Polatuzumab ... This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with rituximab, gemcitabine and ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.7551

Initial safety run-in results of the phase III POLARGO trial A Phase III, multicenter, open-label, randomized trial evaluating the safety and efficacy of Pola-R-GemOx vs R-GemOx in pts with R/R DLBCL.