Mosunetuzumab + Polatuzumab Vedotin for Aggressive B-Cell Lymphoma

(SUNMO Trial)

Recruiting at 93 trial locations

Overseen By Reference Study ID number: GO43643 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Antilymphoma agents, Monoclonal antibodies

Disqualifiers: Pregnancy, CNS disease, Cardiovascular, 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: 1

Duration: 16-24 weeks

242 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will assess the efficacy and safety of mosunetuzumab in combination with polatuzumab vedotin (M+P) in participants with relapsed or refractory (R/R) diffuse-large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, transformed follicular lymphoma (trFL) and FL Grade 3B (FL3B) in comparison with a commonly used regimen in this participant population, rituximab, gemcitabine and oxaliplatin (R-GemOx).

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have received certain anti-lymphoma treatments or other investigational therapies shortly before starting the study treatment.

What data supports the effectiveness of the drug combination Mosunetuzumab and Polatuzumab Vedotin for treating aggressive B-cell lymphoma?

Polatuzumab vedotin, when combined with rituximab, has shown significant clinical activity in treating relapsed or refractory diffuse large B-cell lymphoma, which is a type of aggressive B-cell lymphoma. This combination has been effective in patients who have not responded to other treatments, suggesting potential effectiveness for similar conditions. ^{1 2 3 4 5}

Is the combination of Mosunetuzumab and Polatuzumab Vedotin safe for humans?

Polatuzumab vedotin has been studied in various clinical trials for B-cell lymphomas, and the risk of developing anti-drug antibodies (which can affect how the body responds to the drug) is considered low. This suggests that the treatment is generally safe for humans, as the low incidence of these antibodies is not expected to impact the overall safety profile. ^{1 5 6 7 8}

What makes the drug combination of Mosunetuzumab and Polatuzumab Vedotin unique for treating aggressive B-cell lymphoma?

This treatment is unique because it combines Mosunetuzumab, a bispecific antibody that targets CD20 and CD3 to engage T-cells, with Polatuzumab Vedotin, an antibody-drug conjugate targeting CD79b on B-cells, offering a novel dual-targeting approach that may enhance the immune system's ability to attack lymphoma cells. ^{1 2 7 8 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with certain aggressive B-cell non-Hodgkin's lymphomas that have come back or didn't respond to previous treatments. They should be relatively active (ECOG 0-2), not eligible for stem cell transplant if only one prior therapy was received, and must have measurable disease. People with HIV can join if stable on treatment, but those with recent other cancer treatments, major infections, heart or lung issues, CNS involvement of lymphoma, severe allergies to monoclonal antibodies or autoimmune diseases cannot participate.

Inclusion Criteria

My cancer can be measured by tests.

I can take care of myself and am up and about more than half of my waking hours.

My liver, blood, and kidney functions are all within normal ranges.

Exclusion Criteria

I have a history of CNS disease but have been stable for the past 2 years without medication.

I do not have severe heart problems like recent heart attacks or unstable heart rhythms.

I haven't had treatments like monoclonal antibodies for my lymphoma in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mosunetuzumab and polatuzumab vedotin or rituximab, gemcitabine, and oxaliplatin over multiple cycles

16-24 weeks

Multiple visits per cycle, including Days 1, 8, and 15 for Cycle 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Mosunetuzumab
• Polatuzumab vedotin
• Rituximab

Trial Overview The study tests the effectiveness and safety of mosunetuzumab combined with polatuzumab vedotin against a standard regimen of rituximab plus gemcitabine and oxaliplatin in participants with relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma. It aims to see which combination works better for these conditions.

Participant Groups

Group I: M+P (Arm A) Experimental Treatment 3 Interventions

Participants will receive subcutaneous (SC) mosunetuzumab plus intravenous (IV) polatuzumab vedotin (M+P). Mosunetuzumab will be administered on Days 1, 8, and 15 of Cycle 1, and thereafter on Day 1 of Cycles 2-8. Polatuzumab vedotin will be administered on Day 1 of each cycle up to Cycle 6. Cycle length = 21 days.

Group II: R-GemOx (Arm B) Active Control 3 Interventions

Participants will receive IV rituximab, IV gemcitabine, and IV oxaliplatin (R-GemOx) on Day 1 of each cycle for 8 cycles. Cycle length = 14 days.

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 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]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has shown significant clinical efficacy in treating relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and received accelerated FDA approval for use in patients who have failed at least two prior therapies.

The drug is currently being evaluated in combination with other therapies for previously untreated DLBCL patients, indicating its potential to play a broader role in the treatment of this heterogeneous disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin: Current Role and Future Applications in the Treatment of Patients with Diffuse Large B-Cell Lymphoma. Assi, R., Masri, N., Dalle, IA., et al.[2021]

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 (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, 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]

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]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has demonstrated significant clinical effectiveness in treating follicular and diffuse large B-cell lymphoma (DLBCL), and is FDA-approved for use with bendamustine and rituximab in patients with relapsed or refractory DLBCL.

The review highlights the ongoing research and potential future applications of polatuzumab in the treatment of B-cell non-Hodgkin lymphoma, indicating its importance in expanding treatment options for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of Polatuzumab Vedotin in the Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma: A Brief Report on the Emerging Clinical Data. Sawalha, Y., Maddocks, K.[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. England pubmed.ncbi.nlm.nih.gov

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

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

Polatuzumab Vedotin: Current Role and Future Applications in the Treatment of Patients with Diffuse Large B-Cell Lymphoma. [2021]

5. 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]

6. 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]

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

Polatuzumab Vedotin: First Global Approval. [2023]

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

Profile of Polatuzumab Vedotin in the Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma: A Brief Report on the Emerging Clinical Data. [2022]