Zilovertamab Vedotin + R-CHP vs Polatuzumab Vedotin + R-CHP for Lymphoma

Recruiting at 77 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antiretrovirals, HBV antivirals

Must not be taking: Corticosteroids

Disqualifiers: Cardiovascular disease, Peripheral neuropathy, CNS 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: 6

Duration: 4 months

594 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find better ways to treat germinal center B-cell-like diffuse large B-cell lymphoma (GCB DLBCL), a fast-growing blood cancer. Researchers are comparing two treatments: one combines zilovertamab vedotin (an experimental treatment) with other drugs, and the other uses polatuzumab vedotin with the same additional drugs. The goal is to determine which treatment more effectively eliminates cancer. Individuals who have not yet received treatment for their GCB DLBCL and have PET-positive disease may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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, if you are on ongoing corticosteroid therapy, you may not be eligible to participate.

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

In earlier studies, the combination of zilovertamab vedotin with R-CHP showed very promising results. All patients who received a dose of 1.75 mg/kg had a complete response, meaning their cancer was no longer detectable. This outcome suggests the treatment was well-tolerated, as patients responded positively without major issues.

Research from the POLARIX study demonstrated that polatuzumab vedotin with R-CHP is a safe and effective treatment for DLBCL, a type of lymphoma. This combination helped patients live longer without their cancer worsening, indicating it is generally well-tolerated.

Both treatments have shown good results in past studies, suggesting they are safe for people. However, all treatments can have some side effects, so discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard lymphoma treatments that usually involve chemotherapy and monoclonal antibodies, researchers are excited about zilovertamab vedotin and polatuzumab vedotin because they offer a unique mechanism of action. Both of these treatments combine an antibody with a chemotherapy agent, allowing them to deliver the cancer-killing drug directly to cancer cells, which may lead to more effective targeting of the disease and potentially fewer side effects. Zilovertamab vedotin specifically targets the ROR1 protein, which is often found on cancer cells but not normal cells, while polatuzumab vedotin targets CD79b, another protein commonly found on lymphoma cells. This targeted approach is promising because it could enhance treatment effectiveness and improve patient outcomes by sparing more healthy cells.

What evidence suggests that this trial's treatments could be effective for lymphoma?

This trial will compare the effectiveness of two treatment combinations for diffuse large B-cell lymphoma (DLBCL). Research has shown that combining zilovertamab vedotin with R-CHP delivers impressive results in treating DLBCL. In one study, all patients achieved a 100% complete response rate, meaning their cancer completely disappeared with this treatment, indicating strong potential for effectively fighting the cancer.

For participants receiving polatuzumab vedotin plus R-CHP, studies like the POLARIX trial have shown it controls the disease better than some older treatments. It improves progression-free survival, helping prevent the cancer from worsening for a longer period.

In summary, both zilovertamab vedotin and polatuzumab vedotin are being tested in this trial for their promise in treating DLBCL, with zilovertamab vedotin showing particularly high response rates in early research. ^{2 4 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with a specific blood cancer called germinal center B-cell-like diffuse large B-cell lymphoma (GCB DLBCL) who haven't been treated before. They must have a confirmed diagnosis, no active hepatitis unless under control, and their HIV must be well managed if present.

Inclusion Criteria

Has positron emission tomography (PET) positive disease at screening, defined as 4 to 5 on the Lugano 5-point scale

My lymphoma is confirmed as GCB subtype of DLBCL.

I have not received any treatment for my DLBCL.

Exclusion Criteria

I am currently being treated for an infection.

My slow-growing cancer has changed into aggressive large B-cell lymphoma.

I have another cancer that has gotten worse or needed treatment in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either zilovertamab vedotin plus R-CHP or polatuzumab vedotin plus R-CHP for up to 6 cycles, with additional cycles of rituximab for high-risk participants

4 months

6 visits (in-person, every 3 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 87 months

What Are the Treatments Tested in This Trial?

Interventions

• Polatuzumab Vedotin
• Zilovertamab Vedotin

Trial Overview The study compares two treatments for GCB DLBCL: Zilovertamab vedotin combined with R-CHP therapy versus Polatuzumab vedotin with R-CHP. The goal is to see which treatment makes the cancer respond better.

How Is the Trial Designed?

Group I: Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP) Experimental Treatment 8 Interventions

Participants will receive a dose of zilovertamab vedotin (1.75 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 6 cycles (up to approximately 4 months) plus 2 additional cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles (up to approximately 4 months).

Group II: Polatuzumab vedotin + R-CHP Active Control 8 Interventions

Participants will receive a dose of polatuzumab vedotin (1.8 mg/kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar administered by IV infusion on Day 1 of each 3-week cycle for up to 6 cycles (up to approximately 4 months) plus 2 additional cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles (up to approximately 4 months).

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

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

Polatuzumab vedotin, rituximab, cyclophosphamide, ... Although the POLARIX trial demonstrated improved progression-free survival with polatuzumab vedotin (Pola) combined with R-CHP (Pola-R-CHP), its ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39832983/

Is first-line treatment with polatuzumab vedotin-rituximab- ... Conclusions: Pola-R-CHP is not cost-effective in the first-line treatment for previously untreated CD20-positive DLBCL in China. A value-based ...

3. 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 ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2115304

Polatuzumab Vedotin in Previously Untreated Diffuse ... Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone ...

5. 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 ...

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

Efficacy and Safety of Polatuzumab Vedotin Plus Rituximab ... This large real-world study supports Pola-R-CHP as an effective frontline option for DLBCL, with sustained efficacy versus R-CHOP observed in unselected ...

7. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper197938.html

Paper: Five-Year Analysis of the POLARIX Study Pola-R-CHP showed a significant progression-free survival (PFS) benefit vs R-CHOP in patients (pts) with intermediate- or high-risk DLBCL at a median follow-up ...