Mosunetuzumab for Lymphoma

(GOLD Trial)

Overseen By Clinical Trials Office

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Danielle Wallace

Must not be taking: Immunosuppressants, Investigational drugs

Disqualifiers: CNS lymphoma, Cardiovascular 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: Unknown

Duration: 18 weeks

40 Participants Needed

Trial Summary

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, you cannot take certain immunosuppressive medications within 2 weeks before starting the trial, except for some specific cases like inhaled corticosteroids or low doses of dexamethasone.

What data supports the effectiveness of the drug Mosunetuzumab for treating lymphoma?

Research shows that Mosunetuzumab, a drug used for relapsed or refractory follicular lymphoma, has an overall response rate of 80% and a complete response rate of 60% in patients who have tried at least two other treatments. This suggests it is a promising option for those with this type of lymphoma. ^{1 2 3 4 5}

Is mosunetuzumab safe for humans?

Mosunetuzumab has been generally well tolerated in clinical trials for patients with relapsed or refractory B-cell lymphomas, including follicular lymphoma. It has been tested in various studies, showing it is safe for human use in these conditions. ^{1 2 3 4 6}

How is the drug mosunetuzumab different from other treatments for lymphoma?

Mosunetuzumab is unique because it is a bispecific antibody that targets both CD20 and CD3, redirecting T cells to attack and eliminate cancerous B cells in lymphoma. Unlike some other treatments, it offers a new option for patients with relapsed or refractory follicular lymphoma, especially those who have not responded to at least two prior therapies, and it has shown high response rates with manageable side effects. ^{2 3 4 7 8}

What is the purpose of this trial?

Older patients with diffuse large B- cell lymphoma (DLBCL) do not have the same rates of disease control as younger patients and are at risk for toxicity. Identifying which patients might benefit from more therapy at the end of first-line treatment is important. The ability to measure small amounts of persistent lymphoma (circulating tumor DNA or ctDNA) might allow the investigators to risk stratify patients. If older patients have detectable ctDNA in the blood at the end of six cycles of polatuzumab vedotin, rituximab and dose-attentuated CHP chemotherapy, patients will receive a bispecific antibody called mosunetuzumab. The investigators hypothesize this will result in "clearing" the ctDNA from the blood and result in better disease control and outcomes for patients. The study will also measure the safety of this regimen and the impact on the function of these older patients utilizing a tool called the geriatric assessment.

Eligibility Criteria

This trial is for older patients with diffuse large B-cell lymphoma (DLBCL) who still have detectable circulating tumor DNA (ctDNA) after six cycles of initial chemotherapy. It's designed to see if additional treatment with mosunetuzumab can help clear the ctDNA and improve outcomes.

Inclusion Criteria

I can take care of myself and am up and about more than half of the day.

Signed Informed Consent Form

I have a biopsy-confirmed histologic transformation and haven't had anthracycline-based treatments.

Exclusion Criteria

I have mild to severe nerve damage in my hands or feet.

I am HIV positive but stable on treatment, with no recent severe infections.

I have been treated with anthracycline before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 cycles of polatuzumab vedotin, rituximab, and dose-attenuated CHP chemotherapy

18 weeks

Consolidation

Participants with detectable ctDNA receive 6 cycles of mosunetuzumab consolidation therapy

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Mosunetuzumab

Trial Overview The study tests whether mosunetuzumab, a bispecific antibody, given after initial chemo can eliminate remaining ctDNA in older DLBCL patients. The goal is to enhance disease control by adding this consolidation therapy at the end of first-line treatment.

Participant Groups

Group I: ctDNA positive Experimental Treatment 1 Intervention

Patients who have achieved a radiographic complete response (CR) on PET/CT, but have detectable ctDNA at the end of treatment with pola-R-mini-CHP will receive 6 cycles of mosunetuzumab consolidation. Patients who have achieved a CR with undetectable ctDNA will be observed. Patients with a partial response on PET/CT will be managed per protocol.

Who Is Running the Clinical Trial?

Danielle Wallace

Lead Sponsor

Trials

1

Recruited

40+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Adaptive Biotechnologies

Industry Sponsor

Trials

14

Recruited

3,700+

Lymphoma Research Foundation

Collaborator

Trials

4

Recruited

130+

Findings from Research

In a study comparing 90 patients from a mosunetuzumab clinical trial to 158 patients from real-world data, mosunetuzumab showed higher overall response (80% vs. 75%) and complete response rates (60% vs. 33%) in treating relapsed/refractory follicular lymphoma.

The results indicate that mosunetuzumab provides a clinically meaningful benefit as a chemotherapy-free treatment option, with better progression-free survival and overall survival outcomes compared to the real-world cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy. McGough, SF., Shamas, N., Wang, J., et al.[2023]

In a phase 2 study involving 90 patients with relapsed or refractory follicular lymphoma, mosunetuzumab achieved a complete response rate of 60%, significantly higher than the historical control rate of 14% with copanlisib, demonstrating its efficacy in this patient population.

The treatment was well tolerated, with the most common side effect being cytokine release syndrome, primarily mild to moderate in severity, and no treatment-related fatalities, indicating a favorable safety profile for outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Budde, LE., Sehn, LH., Matasar, M., et al.[2022]

In a first-in-human trial involving 230 patients with relapsed or refractory B-cell non-Hodgkin lymphomas, mosunetuzumab demonstrated a manageable safety profile with common side effects like neutropenia and cytokine release syndrome, mostly low-grade and occurring primarily in the first treatment cycle.

The treatment showed promising efficacy, with overall response rates of 34.9% for aggressive and 66.2% for indolent B-NHL, and complete response rates of 19.4% and 48.5%, respectively, indicating that mosunetuzumab can induce durable responses in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study. Budde, LE., Assouline, S., Sehn, LH., et al.[2023]

Mosunetuzumab, the first bispecific antibody approved for lymphoma, shows significant efficacy in treating relapsed or refractory follicular lymphoma, with an overall response rate of 80% and a complete response rate of 60%.

The approval of mosunetuzumab was based on a phase 2 trial involving patients who had undergone at least two prior lines of systemic therapy, highlighting its potential as a new treatment option for challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. Cao, Y., Marcucci, EC., Budde, LE.[2023]

In a Phase I study involving 23 Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma, mosunetuzumab was found to be well tolerated, with no deaths reported and manageable side effects, primarily neutropenia and cytokine release syndrome.

The treatment showed promising antitumor activity, with 2 patients achieving complete responses and 11 achieving partial responses, indicating its potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalation part of Phase I study of single-agent mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Munakata, W., Izutsu, K., Mishima, Y., 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]

References

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

Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy. [2023]

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

Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. [2022]

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

Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study. [2023]

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

Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. [2023]

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

Bispecific Antibody Takes Down FL. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Dose-escalation part of Phase I study of single-agent mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma. [2023]

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

Mosunetuzumab: First Approval. [2022]

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

Targeted Treatment of Relapsed or Refractory Follicular Lymphoma: Focus on the Therapeutic Potential of Mosunetuzumab. [2023]