Mosunetuzumab + Polatuzumab for Non-Hodgkin Lymphoma

Recruiting at 30 trial locations

Overseen By Reference Study ID Number: GO40516 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must be taking: Anti-CD20 therapy

Must not be taking: Monoclonal antibodies

Disqualifiers: CNS disease, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

422 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of intravenous (IV) or subcutaneous (SC) mosunetuzumab in combination with polatuzumab vedotin in participants with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). It will consist of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with relapsed or refractory (R/R) DLBCL and 2L+ R/R FL. In addition, subcutaneous mosunetuzumab in combination with polatuzumab vedotin will be evaluated in participants with at least 2 prior lines of systemic therapy (3L+) for the treatment of R/R mantle cell lymphoma (MCL) and in participants with 2L+ R/R DLBCL.

Will I have to stop taking my current medications?

The trial requires that you stop taking any chemotherapeutic or anti-cancer agents at least 4 weeks before starting the study treatment. If you are on any monoclonal antibodies or similar treatments, you must stop them 4 weeks before the trial as well.

What data supports the effectiveness of the drug Mosunetuzumab + Polatuzumab for Non-Hodgkin Lymphoma?

Polatuzumab vedotin, part of the treatment, has shown effectiveness in treating diffuse large B-cell lymphoma, a type of Non-Hodgkin Lymphoma, especially when combined with other drugs like rituximab. It has been approved for use in patients who have not responded to other treatments, demonstrating its potential in managing difficult cases. ^{1 2 3 4 5}

Is the combination of Mosunetuzumab and Polatuzumab safe for humans?

The combination of Mosunetuzumab and Polatuzumab vedotin has been studied in patients with relapsed or refractory large B-cell lymphoma, showing a favorable safety profile. Common side effects included neutropenia (low white blood cell count) and fatigue, with some patients experiencing cytokine release syndrome (a reaction from immune cells). Overall, the treatment is considered to have a manageable safety profile. ^{1 3 6 7 8}

What makes the drug Mosunetuzumab + Polatuzumab vedotin unique for treating Non-Hodgkin Lymphoma?

This drug combination is unique because it uses polatuzumab vedotin, an antibody-drug conjugate that specifically targets CD79b on B-cells, delivering a potent toxin directly to cancer cells, which may reduce side effects compared to traditional chemotherapy. Additionally, combining it with mosunetuzumab, which targets CD20, offers a dual-targeted approach that could enhance effectiveness against lymphoma. ^{1 2 4 7 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with certain types of B-cell non-Hodgkin lymphoma who have tried at least one prior treatment. Specifically, it's for those with relapsed or refractory diffuse large B-cell, follicular, or mantle cell lymphoma. Participants should be in a stable enough condition to perform daily activities (ECOG PS 0-2) and must not have had recent CAR-T therapy, stem cell transplants, or certain other treatments.

Inclusion Criteria

I can take care of myself and perform daily activities.

My cancer is either follicular lymphoma, diffuse large B-cell lymphoma, or mantle cell lymphoma.

I have had treatment with an anti-CD20 therapy for my lymphoma.

Exclusion Criteria

I have had a stem cell transplant from a donor.

I have a confirmed history of PML.

I have or had brain lymphoma or disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Participants will receive mosunetuzumab in combination with polatuzumab vedotin. Dose finding will be guided by the observed incidence of dose-limiting toxicities (DLTs) at each dose level.

8-12 weeks

Expansion Phase

Participants with relapsed or refractory DLBCL and FL will receive mosunetuzumab and polatuzumab vedotin to evaluate safety and efficacy.

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Mosunetuzumab
• Polatuzumab vedotin

Trial Overview The study tests Mosunetuzumab given via IV or SC injection combined with Polatuzumab Vedotin. It starts by finding the right doses and then expands to treat more patients. The goal is to see how safe and effective this combo is for second-line treatment of relapsed/refractory B-cell non-Hodgkin lymphomas.

Participant Groups

Group I: Mosunetuzumab SC + Polatuzumab Vedotin 3L+R/R MCL Experimental Treatment 3 Interventions

Participants with at least 2 lines of prior therapy (3L+) will receive subcutaneous (SC) mosunetuzumab + polatuzumab vedotin.

Group II: Mosunetuzumab SC + Polatuzumab Vedotin 2L+R/R DLBCL Experimental Treatment 3 Interventions

2L+ participants with R/R DLBCL will receive SC mosunetuzumab and polatuzumab vedotin.

Group III: Mosunetuzumab + Polatuzumab Vedotin 2L+R/R DLBCL Experimental Treatment 4 Interventions

2L+ participants with R/R diffuse large B-cell lymphoma will receive mosunetuzumab + polatuzumab vedotin.

Group IV: Mosunetuzumab + Polatuzumab Vedotin 2L+ R/R FL Experimental Treatment 3 Interventions

Participants with at least one line of prior therapy (2L+) and that have relapsed or refractory (R/R) follicular lymphoma (FL) will receive mosunetuzumab + polatuzumab vedotin.

Group V: Dose Finding Experimental Treatment 3 Interventions

Participants will receive mosunetuzumab in combination with polatuzumab vedotin. Dose finding will be guided by the observed incidence of dose-limiting toxicities (DLTs) at each dose level.

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

Approved in European Union as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Approved in United States as Lunsumio for:

• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

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 a study involving 85 patients with untreated diffuse large B-cell lymphoma, the combination of polatuzumab vedotin with standard chemotherapy (R-CHP or G-CHP) showed promising preliminary efficacy, with 89% of patients achieving an overall response and 77% achieving a complete response.

The safety profile of polatuzumab vedotin was manageable, with common adverse events including neutropenia and peripheral neuropathy, leading to the establishment of a recommended phase 2 dose of 1.8 mg/kg for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Tilly, H., Morschhauser, F., Bartlett, NL., et al.[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]

Polatuzumab vedotin (POLIVY®) is an effective treatment for adult patients with diffuse large B-cell lymphoma, approved after showing significant anti-cancer activity by delivering a potent drug directly to B cells.

The incidence of anti-drug antibodies (ADA) against polatuzumab vedotin is low, likely due to its mechanism of action that targets and kills B cells, which minimizes immune response and supports a favorable benefit/risk profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Dere, RC., Beardsley, RL., Lu, D., et al.[2023]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, shows promise in treating relapsed or refractory B-cell non-Hodgkin lymphomas, particularly when combined with rituximab and bendamustine, as indicated by early clinical data.

The ongoing phase III POLARIX trial is exploring its effectiveness in first-line treatment for untreated patients, with careful management of dosing to minimize the risk of peripheral neuropathy, potentially making it a key player in DLBCL therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin: an investigational anti-CD79b antibody drug conjugate for the treatment of diffuse large B-cell lymphoma. Bourbon, E., Salles, G.[2022]

In a study of 57 patients with relapsed large B-cell lymphoma after CAR T-cell therapy, polatuzumab vedotin (PV) showed a response rate of 44%, with 14% achieving complete remission, indicating its potential efficacy in this challenging patient population.

The median progression-free survival was only 10 weeks, and factors like bone marrow involvement and high lactate dehydrogenase levels were linked to shorter survival, highlighting the need for further research on treatment resistance and consolidation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy. Gouni, S., Rosenthal, AC., Crombie, JL., 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]

Polatuzumab vedotin, an antibody-drug conjugate, demonstrated an acceptable safety profile in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL), with a recommended phase 2 dose of 2.4 mg/kg showing objective responses in 23 out of 42 evaluable patients.

In contrast, the treatment was not effective for patients with chronic lymphocytic leukaemia (CLL), as no objective responses were observed, highlighting the need for further assessment of polatuzumab vedotin specifically in NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Palanca-Wessels, MC., Czuczman, M., Salles, G., et al.[2018]

In a phase 1b/2 trial involving 120 patients with relapsed/refractory aggressive large B cell lymphoma, the combination of mosunetuzumab and polatuzumab vedotin achieved a high overall response rate of 59.2% and a complete response rate of 45.9%, indicating strong efficacy as a second-line therapy.

The treatment demonstrated a favorable safety profile, with the most common serious side effects being neutropenia (25%) and fatigue (6.7%), and only 16.7% of patients experiencing any-grade cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Budde, LE., Olszewski, AJ., Assouline, S., et al.[2023]

Polatuzumab vedotin is an antibody-drug conjugate that has shown significant clinical activity and an acceptable safety profile in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), particularly when combined with anti-CD20 monoclonal antibodies and chemotherapy.

The recent POLARIX trial suggests that polatuzumab may also be effective in frontline treatment for DLBCL, potentially changing its role in managing patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. Varma, G., Wang, J., Diefenbach, C.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. [2023]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. [2023]

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

Polatuzumab vedotin: an investigational anti-CD79b antibody drug conjugate for the treatment of diffuse large B-cell lymphoma. [2022]

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

A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy. [2023]

6. 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]

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

Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. [2018]

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

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. [2022]