Mosunetuzumab + Polatuzumab Vedotin for Follicular Lymphoma

Recruiting at 1 trial location

Overseen By Matthew Mei, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Anticancer agents

Disqualifiers: Active infection, Autoimmune disease, 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: 51

Duration: 18-51 weeks

41 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining mosunetuzumab and polatuzumab vedotin to treat follicular lymphoma, a type of blood cancer that has returned or resisted previous treatments. Mosunetuzumab is a targeted antibody against cancer cells, while polatuzumab vedotin is an antibody linked to a toxin that kills cancer cells. The trial aims to determine if this combination can effectively eliminate more cancer cells. Suitable candidates for this trial have follicular lymphoma requiring treatment and have not responded to previous therapies. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on systemic immunosuppressive therapy, it must be reduced to a low dose before starting the trial. It's best to discuss your specific medications with the study team.

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

Research has shown that the combination of mosunetuzumab and polatuzumab vedotin is generally safe. Previous studies found that this treatment works well over time, making it a good option for patients who cannot undergo a transplant. Early trials demonstrated that most people tolerate the combination without serious issues. This suggests the treatment might be safe for those with relapsed or hard-to-treat follicular lymphoma. However, patients should still consult their doctor about possible side effects and risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Mosunetuzumab and Polatuzumab Vedotin for treating follicular lymphoma because they introduce innovative approaches compared to standard treatments like chemotherapy and rituximab. Mosunetuzumab is a bispecific antibody designed to engage both T-cells and cancer cells, enhancing the immune system's ability to attack the lymphoma. Meanwhile, Polatuzumab Vedotin is an antibody-drug conjugate that delivers chemotherapy directly to cancer cells, minimizing damage to healthy cells. Together, these treatments offer a targeted approach that could improve efficacy and reduce side effects, providing new hope for patients with follicular lymphoma.

What evidence suggests that mosunetuzumab and polatuzumab vedotin might be effective for follicular lymphoma?

Research has shown that combining mosunetuzumab and polatuzumab vedotin holds promise for treating certain types of lymphoma, including cases where the cancer has returned or resisted other treatments. For example, in studies with patients who have mantle cell lymphoma, this combination reduced or eliminated cancer in 88% of cases. Another study found that this treatment extended patients' progression-free survival by about 11.5 months, outperforming some other treatments. This trial will evaluate the effectiveness of this combination specifically for follicular lymphoma, aiming to more effectively target and kill cancer cells. ^{1 2 4 6 7}

Who Is on the Research Team?

Matthew Mei, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with grade 1-3a follicular lymphoma that has either relapsed or hasn't responded to previous treatments. Participants should have a type of cancer that the drugs used in this study can target.

Inclusion Criteria

Documented informed consent of the participant and/or legally authorized representative

I have recovered from side effects of previous cancer treatments.

Assent, when appropriate, will be obtained per institutional guidelines

Exclusion Criteria

I do not have active viral infections like HBV, HCV, HIV, or chronic EBV.

I have heart, liver, autoimmune conditions, or had major surgery recently.

I am not on any immune-suppressing drugs, with certain exceptions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive polatuzumab vedotin IV and mosunetuzumab SC in cycles every 21 days for up to 6-17 cycles

18-51 weeks

Visits every 21 days for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Follow-up at 30 days post-treatment and then for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Mosunetuzumab
• Polatuzumab Vedotin

Trial Overview The effectiveness of mosunetuzumab and polatuzumab vedotin is being tested on patients with specific types of follicular lymphoma. The trial involves various diagnostic tests like CT, PET, MRI scans, and questionnaires to monitor progress.

How Is the Trial Designed?

Group I: Treatment (mosunetuzumab, polatuzumab vedotin) Experimental Treatment 7 Interventions

Patients receive polatuzumab vedotin IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and day 1 of remaining cycles. Cycles repeat every 21 days for up to 8-17 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and CT, PET/CT, or MRI throughout the study.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

In a study of 69 patients with aggressive B-cell lymphoma treated with polatuzumab vedotin combined with bendamustine and rituximab, a 50% response rate was observed, with a 24% complete response rate, indicating some efficacy in a real-world setting.

However, the median progression-free survival (PFS) was only 2.0 months, and survival was 5.3 months, which is lower than what was reported in clinical trials, particularly for patients with prior refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin for Relapsed/Refractory Aggressive B-cell Lymphoma: A Multicenter Post-marketing Analysis. Smith, SD., Lopedote, P., Samara, Y., et al.[2022]

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]

Mosunetuzumab, a bispecific antibody targeting CD20 and CD3, has received conditional approval in the EU for treating adults with relapsed or refractory follicular lymphoma after at least two prior therapies.

This approval marks a significant milestone in the development of mosunetuzumab, highlighting its potential as a new treatment option for patients with difficult-to-treat lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab: First Approval. Kang, C.[2022]

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]

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]

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 Pola-G-Len combination therapy demonstrated a high complete response rate of 63% and an overall objective response rate of 76% in patients with relapsed or refractory follicular lymphoma, indicating its potential efficacy in this challenging patient population.

The study identified a recommended phase 2 dose of 1.4 mg/kg polatuzumab vedotin plus 20 mg lenalidomide, with manageable safety profiles, although common adverse events included neutropenia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin plus obinutuzumab and lenalidomide in patients with relapsed or refractory follicular lymphoma: a cohort of a multicentre, single-arm, phase 1b/2 study. Diefenbach, C., Kahl, BS., McMillan, A., et al.[2022]

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]

Citations

1. roche.com roche.com/media/releases/med-cor-2025-06-20

Roche's Lunsumio and Polivy combination significantly ... Pivotal phase III SUNMO study demonstrated an 11.5 month median progression-free survival - three times longer than R-GemOx1 ...

2. onclive.com onclive.com/view/mosunetuzumab-polatuzumab-vedotin-is-an-effective-off-the-shelf-combo-in-r-r-mcl

Off-the-Shelf, Fixed-Duration Combination Is Active in ... Mosunetuzumab and polatuzumab vedotin achieved an 88% overall response rate in relapsed/refractory MCL patients, with a 79% complete response ...

3. nature.com nature.com/articles/s41591-023-02726-5

Mosunetuzumab with polatuzumab vedotin in relapsed or ... Efficacy outcomes in the phase 2 dose-expansion cohort. Ninety-eight patients with R/R LBCL were treated at the 1/2/60/30 mg mosunetuzumab dose ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4414/529974/Mosunetuzumab-Plus-Polatuzumab-Vedotin-Induces

Mosunetuzumab Plus Polatuzumab Vedotin Induces Early ... A phase 1/2 study of Mosun plus Pola in r/r B cell lymphoma showed promising efficacy and a reasonable safety profile (Budde Nat Med 2024).

5. bloodcancerstoday.com bloodcancerstoday.com/post/mosunetuzumab-plus-polatuzumab-shows-broad-efficacy-in-relapsed-mcl

Mosunetuzumab Plus Polatuzumab Shows Broad Efficacy ... In a phase 2 study, the overall response rate was 88%, and the complete response rate 79%. The combination was also effective in high-risk ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06453044

Study Details | NCT06453044 | Mosunetuzumab and ... Giving mosunetuzumab and polatuzumab vedotin may kill more cancer cells in patients with relapsed or refractory grade 1-3a follicular lymphoma. Detailed ...

7. gene.com gene.com/media/press-releases/15069/2025-06-20/genentechs-lunsumio-and-polivy-combinati

Genentech: Press Releases | Friday, Jun 20, 2025 Pivotal Phase III SUNMO study demonstrated an 11.5 month median progression-free survival – three times longer than R-GemOx.