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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called mosunetuzumab, a type of immunotherapy, for older patients with diffuse large B-cell lymphoma (DLBCL). The researchers aim to determine if this treatment can better control the disease by targeting small traces of cancer in the blood after initial treatment. Participants who have completed certain chemotherapy sessions and still have cancer markers in their blood may receive mosunetuzumab to improve outcomes. This trial suits individuals aged 70 or older with DLBCL who have not fully responded to initial treatments. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering a chance to potentially benefit from an innovative therapy.

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.

Is there any evidence suggesting that mosunetuzumab is likely to be safe for humans?

Research has shown that mosunetuzumab has been tested for safety in people with non-Hodgkin lymphoma, yielding promising results. In previous studies, mosunetuzumab was generally well-tolerated, with most participants not experiencing severe reactions. The most common side effects included tiredness and fever, typically mild to moderate. Some participants experienced more serious effects, such as low blood cell counts, but these were less common.

These studies provide a good understanding of mosunetuzumab's safety, but it remains under investigation and is not yet approved for all uses. Researchers continue to study its safety, particularly in older individuals with diffuse large B-cell lymphoma. Prospective trial participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for lymphoma?

Unlike the standard treatments for lymphoma, which often include chemotherapy and targeted drugs, mosunetuzumab is a bispecific antibody that targets both CD20 on B cells and CD3 on T cells. This dual targeting mechanism is unique because it brings the patient's own T cells directly to the cancerous B cells, potentially enhancing the immune system's ability to fight the cancer more effectively. Researchers are excited about mosunetuzumab because it offers a new approach that could be more efficient and possibly result in fewer side effects than traditional chemotherapy. Additionally, it provides an opportunity for patients who have residual disease detected by ctDNA to receive further treatment that targets these cancer cells specifically.

What evidence suggests that mosunetuzumab might be an effective treatment for lymphoma?

Research has shown that mosunetuzumab, which participants in this trial may receive, effectively treats certain types of lymphoma. Studies have found that about 80% of patients experience a reduction in their cancer, and around 60% achieve a complete response, meaning no signs of cancer are detectable. The treatment demonstrated promising results in patients previously treated for lymphoma, with long-lasting remissions and manageable safety concerns. These findings suggest mosunetuzumab could be a good option for older patients with diffuse large B-cell lymphoma, especially when traditional treatments might not work as well. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

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

My lymphoma has both slow-growing and aggressive features.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: ctDNA positive Experimental Treatment 2 Interventions

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+

Published Research Related to This Trial

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]

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]

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, 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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/145/7/708/525779/Long-term-3-year-follow-up-of-mosunetuzumab-in

Long-term 3-year follow-up of mosunetuzumab in relapsed or ... Three-year follow-up of mosunetuzumab in R/R FL after ≥2 prior therapies showed long-lasting remissions and meaningful survival outcomes.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11210942/

Durable Responses With Mosunetuzumab in Relapsed ... This analysis evaluates the long-term efficacy and safety outcomes of mosunetuzumab, as well as the re-treatment experience across lines of ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497124107719

Long-term 3-year follow-up of mosunetuzumab in relapsed ... With extended follow-up, mosunetuzumab demonstrated high response rates, durable remissions and manageable safety with no long-term concerns.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e19013

Efficacy and safety of mosunetuzumab-based regimens as ... Conclusions: Mosunetuzumab with CHOP showed higher efficacy results and was well tolerated by most of the patients and can be an option to ...

5. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01462-0

Mosunetuzumab and lymphoma: latest updates from 2022 ... Mosunetuzumab demonstrated remarkable efficacy with an overall response rate of 80% and complete response rate of 60%. Here we provided an ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38195322/

Mosunetuzumab Safety Profile in Patients With Relapsed ... Materials and methods: We present interim safety data from the mosunetuzumab GO29781 (NCT02500407) phase I/II dose-escalation study in R/R non-Hodgkin lymphoma ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2152265023021948

Mosunetuzumab Safety Profile in Patients With Relapsed ... We present interim safety data from the mosunetuzumab GO29781 (NCT02500407) phase I/II dose-escalation study in R/R non-Hodgkin lymphoma (NHL), focusing on FL.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02500407

Study Details | NCT02500407 | A Safety, Efficacy and ... A Safety, Efficacy and Pharmacokinetic Study of BTCT4465A (Mosunetuzumab) as a Single Agent and Combined With Atezolizumab in Non-Hodgkin's Lymphoma (NHL) and ...