Mosunetuzumab + Polatuzumab Vedotin for Aggressive B-Cell Lymphoma

(SUNMO Trial)

Not currently recruiting at 110 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments, mosunetuzumab and polatuzumab vedotin, for individuals with aggressive B-cell lymphoma, a type of blood cancer that has returned or not responded to previous treatment. The goal is to determine if these new treatments are more effective and safer than the standard regimen of rituximab, gemcitabine, and oxaliplatin. Eligible participants have aggressive lymphoma that has recurred or not responded to at least one prior treatment and are ineligible for a stem cell transplant. The trial evaluates whether the new combination can better manage the disease for those with difficult-to-treat lymphoma. As a Phase 3 trial, this study serves as the final step before FDA approval, offering patients access to potentially groundbreaking treatments.

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.

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

Research has shown that using mosunetuzumab and polatuzumab vedotin together is generally safe. In studies, patients experienced long-lasting positive responses, indicating the treatment remained effective over time. This combination offers a viable option for patients ineligible for stem cell transplants.

Mosunetuzumab, a monoclonal antibody, may help stop cancer cells from growing and spreading. Polatuzumab vedotin, another monoclonal antibody, works similarly. The FDA has already approved mosunetuzumab for certain types of lymphoma, a cancer of the lymphatic system, confirming its safety in similar conditions.

Overall, these treatments are usually well-tolerated, with side effects that most patients can manage. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because mosunetuzumab and polatuzumab vedotin offer new strategies for tackling aggressive B-cell lymphoma. Unlike traditional options like R-CHOP, which use a combination of chemotherapy drugs, mosunetuzumab is a bispecific antibody that targets CD20 and CD3, potentially leading to a more direct attack on cancer cells by engaging the immune system. Polatuzumab vedotin, on the other hand, combines an antibody with a chemotherapy agent, delivering the drug directly to the cancer cells, which may reduce side effects and improve effectiveness. This dual approach could offer a more targeted and potentially less toxic treatment option compared to conventional therapies.

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

Research has shown that the combination of mosunetuzumab and polatuzumab vedotin, which participants may receive in the M+P arm of this trial, holds promise for treating aggressive B-cell lymphomas, such as diffuse-large B-cell lymphoma (DLBCL). Studies have found this treatment to be generally safe with long-lasting effects. It is considered a good option for patients who did not respond well to their initial treatment. Early results suggest that this therapy can benefit individuals with limited options, particularly those unable to undergo more intense treatments. ^{1 2 6 7 8}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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]

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, 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 (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 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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38072960/

Mosunetuzumab with polatuzumab vedotin in relapsed or ... These data demonstrate that mosunetuzumab plus polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10803244/

Mosunetuzumab with polatuzumab vedotin in relapsed or ... These data demonstrate that mosunetuzumab plus polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as second-line therapy ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05633615

NCT05633615 | Testing Drug Treatments After CAR T-cell ... This phase II trial tests whether mosunetuzumab and/or polatuzumab vedotin helps benefit patients who have received chemotherapy (fludarabine and ...

4. ash.confex.com ash.confex.com/ash/2023/webprogram/Paper174209.html

Paper: Mosunetuzumab Plus Polatuzumab Vedotin ... The ongoing Phase Ib/II GO40516 study (NCT03671018) investigates Mosun in combination with polatuzumab vedotin (Pola; M-Pola) in pts with B-cell ...

5. esmo.org esmo.org/oncology-news/mosunetuzumab-plus-polatuzumab-vedotin-shows-promise-for-patients-with-aggressive-relapsed-or-refractory-aggressive-large-b-cell-lymphoma

Mosunetuzumab Plus Polatuzumab Vedotin Shows ... Mosunetuzumab in combination with polatuzumab vedotin holds promise for patients with aggressive relapsed or refractory large B cell lymphoma ineligible for ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/761121Orig1s008MultidisciplineR.pdf

761121Orig1s008 MULTI-DISCIPLINE REVIEW Summary ... B-Cell-Like Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2018;37(3): ... Polatuzumab Vedotin (DCDS4501A) in Combination With Rituximab or ...

7. ckb-core.genomenon.com ckb-core.genomenon.com/therapy/show/7623

Therapy Detail - CKB CORE - Genomenon Lunsumio (mosunetuzumab-axgb) is FDA approved for use in adult patients with relapsed or refractory follicular lymphoma who have received two or more lines of ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2213048921000492

Novel biologic therapies in relapsed or refractory diffuse ... Subcutaneous Mosunetuzumab in relapsed or refractory B-cell lymphoma: promising safety and encouraging efficacy in dose escalation cohorts. Blood, 136 ...