Zilovertamab Vedotin + R-CHP for Lymphoma

Recruiting at 123 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antiretroviral, HBV antiviral

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)

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: 6

Duration: 4 months

1046 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate if zilovertamab vedotin with standard treatment can help people live longer without the cancer growing or spreading than people who receive standard treatment alone.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, ongoing corticosteroid therapy is not allowed, and certain conditions like active infections or cardiovascular issues may require medication adjustments.

What data supports the effectiveness of the drug combination Zilovertamab Vedotin + R-CHP for Lymphoma?

The combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been shown to improve outcomes in patients with non-Hodgkin's lymphoma, and rituximab maintenance therapy significantly improves progression-free survival. Additionally, rituximab added to CHOP improves outcomes in diffuse large B-cell lymphoma, suggesting potential effectiveness when combined with other agents like Zilovertamab Vedotin. ^{1 2 3 4 5}

Is Zilovertamab Vedotin + R-CHP safe for humans?

The combination of brentuximab vedotin (similar to Zilovertamab Vedotin) with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) has been studied in patients with certain types of lymphoma. In these studies, there were no treatment-related deaths, but some patients experienced serious side effects. Overall, the treatment was considered feasible with manageable side effects. ^{6 7 8 9 10}

What makes Zilovertamab Vedotin + R-CHP unique for lymphoma treatment?

Zilovertamab Vedotin + R-CHP is unique because it combines a novel antibody-drug conjugate (Zilovertamab Vedotin) with a standard chemotherapy regimen (R-CHP), potentially offering a new mechanism of action by targeting specific proteins on cancer cells, which may improve outcomes compared to traditional chemotherapy alone. ^{7 8 11 12 13}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with previously untreated Diffuse Large B-Cell Lymphoma (DLBCL). They must be in fairly good health (ECOG 0-2), have a heart ejection fraction of at least 45%, and if HIV or hepatitis C positive, these conditions must be well-managed. Those with active hepatitis B are excluded.

Inclusion Criteria

I have not received any treatment for my DLBCL.

Has an ejection fraction ≥45% as determined by either echocardiogram (ECHO) or multigated acquisition (MUGA)

I have HIV and it is well controlled with medication.

Exclusion Criteria

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

I have active lymphoma in my brain or spinal cord.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zilovertamab vedotin with R-CHP or R-CHOP for up to 6 cycles

4 months

6 visits (in-person, every 21 days)

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 74 months

Treatment Details

Interventions

• Cyclophosphamide
• Doxorubicin
• Prednisone
• Rituximab
• Zilovertamab Vedotin

Trial Overview The study tests whether Zilovertamab Vedotin combined with R-CHP therapy improves outcomes compared to the standard R-CHOP therapy in treating DLBCL. Participants will randomly receive either the new combination or the standard treatment to compare effectiveness.

Participant Groups

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

Participants 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 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day cycle for up to 6 cycles (up to approximately 4 months).

Group II: Rituximab + Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP) Active Control 8 Interventions

Participants receive 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar, 1.4 mg/m\^2 vincristine administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 6 cycles (up to approximately 4 months). Participants also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 21-day 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

Findings from Research

The addition of rituximab to standard chemotherapy regimens like CHOP and ACVBP significantly improves treatment outcomes for lymphoma patients, allowing for fewer cycles of treatment without compromising efficacy.

Using positron emission tomography (PET) scans early in treatment can help predict long-term outcomes, enabling personalized treatment plans based on individual patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current approaches to the treatment of non-Hodgkin's lymphoma. Gisselbrecht, C.[2021]

In a study involving 602 elderly patients with untreated diffuse large B-cell lymphoma, the dose-dense R-CHOP regimen administered every 2 weeks (R-CHOP14) did not show improved event-free survival compared to the standard 3-week schedule (R-CHOP21), with 3-year event-free survival rates of 56% and 60% respectively.

Although both regimens had similar rates of serious adverse events, the R-CHOP14 group experienced a significantly higher need for red-blood-cell transfusions (47% vs. 31% in R-CHOP21), indicating a potential drawback of the more frequent dosing schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Delarue, R., Tilly, H., Mounier, N., et al.[2022]

The combination of rituximab with the chemotherapy regimen CVP (R-CVP) significantly improves life expectancy and quality-adjusted life years (QALYs) in previously untreated patients with indolent non-Hodgkin lymphoma, compared to CVP alone, with increases of 0.804 life years gained and 0.728 QALYs.

Despite R-CVP having a higher total cost per patient (€87,774 vs. €85,838 for CVP), it is considered cost-effective, with an incremental cost of €2,661 per QALY gained, indicating that the benefits in survival and quality of life justify the additional expense.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Economic analysis of rituximab in combination with cyclophosphamide, vincristine and prednisolone in the treatment of patients with advanced follicular lymphoma in Portugal]. Braga, P., Carvalho, S., Gomes, M., et al.[2015]

In a study of 250 patients with indolent non-Hodgkin lymphomas, both R-CVP and R-CHOP regimens followed by rituximab maintenance showed similar efficacy in terms of event-free survival and progression-free survival after a median follow-up of over 5 years.

R-CVP demonstrated significantly lower rates of severe adverse events compared to R-CHOP, making it a safer option for induction treatment in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line R-CVP versus R-CHOP induction immunochemotherapy for indolent lymphoma with rituximab maintenance. A multicentre, phase III randomized study by the Polish Lymphoma Research Group PLRG4. Walewski, J., Paszkiewicz-Kozik, E., Michalski, W., et al.[2020]

In a study of 435 patients with diffuse large B-cell lymphoma (DLBCL), the addition of rituximab to CHOP chemotherapy (R-CHOP) was associated with a reduced risk of central nervous system (CNS) relapse, showing a trend of 6.4% risk in R-CHOP patients compared to 9.7% in those treated with CHOP.

Rituximab significantly lowered the risk of CNS relapse (hazard ratio 0.45) and this benefit was even greater for patients who achieved a complete response (hazard ratio 0.18), indicating that R-CHOP is particularly effective in preventing CNS involvement in DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: the impact of the addition of rituximab to CHOP chemotherapy. Villa, D., Connors, JM., Shenkier, TN., et al.[2022]

The combination of brentuximab vedotin (BV) with ifosfamide-carboplatin-etoposide (ICE) was found to be safe and effective as a second-line therapy for patients with refractory/relapsed classical Hodgkin lymphoma, with 61.9% achieving a complete metabolic response after 2 cycles.

With a median follow-up of 38 months, the treatment showed promising long-term outcomes, including a 3-year progression-free survival rate of 64.3% and an overall survival rate of 100%, indicating its potential as a viable alternative to other salvage therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of brentuximab vedotin combined with ifosfamide-carboplatin-etoposide in first refractory/relapsed Hodgkin lymphoma: a lymphoma study association phase I/II study. Stamatoullas, A., Ghesquières, H., Feugier, P., et al.[2023]

Brentuximab vedotin (Bv) combined with bendamustine (B) showed a high overall response rate of 79% and a complete response rate of 49% in 47 patients with relapsed or refractory classic Hodgkin lymphoma, indicating its efficacy as a treatment option.

The treatment resulted in a median progression-free survival of 18 months and a 2-year overall survival rate of 72%, particularly benefiting patients who achieved a major clinical response and those who underwent stem cell transplantation afterward.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study. Iannitto, E., Romano, A., Scalzulli, PR., et al.[2021]

Brentuximab vedotin (BV) demonstrated high efficacy in treating relapsed or refractory CD30-positive lymphomas, with an objective response rate of 85.4% for Hodgkin lymphoma, 88% for anaplastic large-cell lymphoma, and 92% for cutaneous T-cell lymphomas, indicating its effectiveness across different lymphoma types.

The safety profile of BV was manageable, with peripheral neuropathy being the most common side effect, affecting 25.9% of patients, suggesting that while side effects occur, they are not severe enough to outweigh the treatment benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multi-center and non-interventional registry of brentuximab vedotin in patients with relapsed or refractory CD30-positive lymphoma: the CISL1803/BRAVO study. Kim, SJ., Do, YR., Lee, HS., et al.[2023]

In a phase I/II trial involving 31 patients with CD30-positive B-cell lymphomas, the combination of brentuximab vedotin and R-CHP resulted in a remarkable overall response rate of 100%, with 86% achieving complete response after treatment.

The treatment was well-tolerated, with no treatment-related deaths and a 2-year progression-free survival rate of 85%, indicating that this regimen is both effective and safe for patients with these types of lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone as frontline treatment for patients with CD30-positive B-cell lymphomas. Svoboda, J., Bair, SM., Landsburg, DJ., et al.[2022]

Recent advances in treating relapsed or refractory classical Hodgkin lymphoma (cHL) include promising immunotherapies like pembrolizumab and nivolumab, as well as CAR T cell therapies, which have shown positive results in early trials.

Novel targeted therapies, such as histone deacetylase inhibitors and Janus kinase 2 inhibitors, are being investigated, indicating a growing array of treatment options that could enhance cure rates and prolong remission for patients with R/R HL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Therapy for Relapsed or Refractory Hodgkin Lymphoma. Choi, Y., Diefenbach, CS.[2021]

Brentuximab vedotin (BV) is an FDA-approved treatment for classic Hodgkin lymphoma (cHL) that is effective after multiple prior treatments, including chemotherapy and stem cell transplantation.

BV is well-tolerated in patients with relapsed or refractory cHL and is also being studied in combination with other treatments for newly diagnosed advanced-stage cHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin and its use in the treatment of advanced Hodgkin's lymphoma. Nikolaenko, L., Nademanee, A.[2021]

Brentuximab vedotin (BV) has significantly improved treatment options for patients with classical Hodgkin lymphoma (cHL) who have relapsed or are refractory to conventional therapies, showing high efficacy in heavily treated patients.

Recent studies, including a phase III trial (ECHELON-1), indicate that BV combined with chemotherapy (AVD) is effective for newly diagnosed advanced-stage cHL, suggesting its potential as a standard treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Brentuximab Vedotin in the Treatment of Classic Hodgkin Lymphoma. Makita, S., Maruyama, D., Tobinai, K.[2023]

Brentuximab vedotin (BV) combined with cyclophosphamide, doxorubicin, and prednisone (BV-CHP) has shown improved outcomes in treating common nodal CD30+ peripheral T-cell lymphomas (PTCLs) compared to the traditional treatment regimen, indicating a significant advancement in therapy.

Further research is needed to determine the optimal level of CD30 expression for effective BV-CHP therapy and to assess its efficacy and safety in less common subtypes of CD30+ PTCLs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in the treatment of CD30+ PTCL. Barta, SK., Gong, JZ., Porcu, P.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Current approaches to the treatment of non-Hodgkin's lymphoma. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. [2022]

3. Portugal pubmed.ncbi.nlm.nih.gov

[Economic analysis of rituximab in combination with cyclophosphamide, vincristine and prednisolone in the treatment of patients with advanced follicular lymphoma in Portugal]. [2015]

4. England pubmed.ncbi.nlm.nih.gov

First-line R-CVP versus R-CHOP induction immunochemotherapy for indolent lymphoma with rituximab maintenance. A multicentre, phase III randomized study by the Polish Lymphoma Research Group PLRG4. [2020]

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

Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: the impact of the addition of rituximab to CHOP chemotherapy. [2022]

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

Final results of brentuximab vedotin combined with ifosfamide-carboplatin-etoposide in first refractory/relapsed Hodgkin lymphoma: a lymphoma study association phase I/II study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study. [2021]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

A multi-center and non-interventional registry of brentuximab vedotin in patients with relapsed or refractory CD30-positive lymphoma: the CISL1803/BRAVO study. [2023]

9. Italy pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone as frontline treatment for patients with CD30-positive B-cell lymphomas. [2022]

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

Advances in Therapy for Relapsed or Refractory Hodgkin Lymphoma. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin and its use in the treatment of advanced Hodgkin's lymphoma. [2021]

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

Safety and Efficacy of Brentuximab Vedotin in the Treatment of Classic Hodgkin Lymphoma. [2023]

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

Brentuximab vedotin in the treatment of CD30+ PTCL. [2021]