Post-CAR T-cell Therapy Drug Combo for Non-Hodgkin's Lymphoma

Recruiting at 81 trial locations

Overseen by Brian T Hess

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: SWOG Cancer Research Network

Must not be taking: Polatuzumab, Mosunetuzumab

Disqualifiers: Cardiac disease, Hepatitis, HIV, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing two treatments, mosunetuzumab and polatuzumab vedotin, for patients with certain types of lymphoma that have come back or don't respond to other treatments. These treatments aim to stop cancer cells from growing or kill them directly. The goal is to see if these treatments can better control or shrink the cancer compared to not using them.

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, you cannot receive polatuzumab vedotin or mosunetuzumab as part of bridging therapy before the trial. It's best to discuss your current medications with the trial team to ensure eligibility.

What data supports the idea that Post-CAR T-cell Therapy Drug Combo for Non-Hodgkin's Lymphoma is an effective treatment?

The available research shows that the combination of mosunetuzumab and polatuzumab vedotin is effective for treating relapsed or refractory aggressive large B-cell lymphoma. In a study, 59.2% of patients responded to the treatment, and 45.9% achieved complete remission. The median time patients lived without the disease getting worse was 11.4 months, and the median overall survival was 23.3 months. This suggests that the drug combo is effective, especially for patients who cannot undergo a transplant. ^{1 2 3 4 5}

What safety data exists for the drug combination used after CAR T-cell therapy in Non-Hodgkin's Lymphoma?

The combination of mosunetuzumab and polatuzumab vedotin has been evaluated in a phase 1b/2 trial for relapsed/refractory large B-cell lymphoma. The most common grade 3 or higher adverse events were neutropenia (25%) and fatigue (6.7%). Any-grade cytokine release syndrome occurred in 16.7% of patients, indicating a favorable safety profile. Polatuzumab vedotin has a low incidence of anti-drug antibodies, suggesting a low immunogenicity risk. In a retrospective study of polatuzumab vedotin after CAR T-cell therapy, 44% of patients responded to treatment, but 81% experienced disease progression or death, with a median progression-free survival of 10 weeks. ^{1 2 3 4 6}

Is the drug used in the trial 'Post-CAR T-cell Therapy Drug Combo for Non-Hodgkin's Lymphoma' a promising treatment?

Yes, the drug polatuzumab vedotin, used in combination with other treatments, shows promise for patients with large B-cell lymphoma, especially those who have relapsed after CAR T-cell therapy. It has been shown to help some patients achieve remission and has been approved for treating certain types of lymphoma. ^{1 2 3 7 8}

Research Team

Brian T Hess

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for adults with certain types of lymphoma (like diffuse large B-cell or follicular grade IIIb) that's come back or isn't responding to treatment. They should be set for CAR T-cell therapy, have a decent performance score, and functioning major organs. People can't join if they've had recent heart issues, used specific drugs as 'bridging' therapy, or if their CAR T-cells aren't FDA-approved.

Inclusion Criteria

I will have a PET-CT scan done within 60 days before starting LD chemotherapy.

My DLBCL cancer developed from follicular or marginal zone lymphoma.

I have HIV, am on effective treatment, and my viral load is undetectable.

Exclusion Criteria

I have moderate to severe numbness, tingling, or pain in my hands or feet.

Participants with disease progression while on Arm 4 (observation) on this protocol

Participants with ANC or platelet counts below specified thresholds

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Patients receive lymphodepleting chemotherapy consisting of fludarabine and cyclophosphamide, followed by CAR T-cell therapy

1-2 weeks

Consolidation Therapy

Patients are randomized to receive mosunetuzumab, polatuzumab vedotin, both, or observation

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Mosunetuzumab (Monoclonal Antibodies)
• Polatuzumab Vedotin (Antibody-Drug Conjugate)

Trial Overview The study tests mosunetuzumab and polatuzumab vedotin in patients who've had chemotherapy followed by CAR T-cell therapy. It aims to see if these drugs help control the cancer better post-CAR T-cell treatment compared to not using them.

Participant Groups

Group I: Step II Arm III (polatuzumab vedotin, mosunetuzumab) Experimental Treatment 5 Interventions

Patients receive polatuzumab vedotin IV and mosunetuzumab IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.

Group II: Step II Arm II (polatuzumab vedotin) Experimental Treatment 4 Interventions

Patients receive polatuzumab vedotin IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.

Group III: Step II Arm I (mosunetuzumab) Experimental Treatment 4 Interventions

Patients receive mosunetuzumab IV on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study.

Group IV: Step I (lymphodepleting chemotherapy) Experimental Treatment 6 Interventions

Patients receive lymphodepleting chemotherapy consisting of fludarabine IV and cyclophosphamide IV on study. Patients then receive tisagenlecleucel IV, axicabtagene ciloleucel IV, or lisocabtagene maraleucel IV on study.

Group V: Step II Arm IV (observation) Active Control 4 Interventions

Patients undergo observation on study. Patients also undergo PET-CT and/or CT and undergo collection of blood and tissue samples throughout the study. Patients with subsequent progression within 12 months of CAR T-cell therapy may crossover to Arm III.

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Dr. Charles D. Blanke

SWOG Cancer Research Network

Chief Executive Officer since 2012

MD from Oregon Health & Science University

Dr. Dawn Hershman

SWOG Cancer Research Network

Chief Medical Officer since 2020

MD from Columbia University

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

Dr. Lyudmila Bazhenova

Southwest Oncology Group

Chief Medical Officer since 2021

MD from University of California, San Diego

Dr. Richard Schilsky

Southwest Oncology Group

Chief Executive Officer since 2013

MD from University of California, San Diego

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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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 phase 1b/2 trial involving 120 patients with relapsed/refractory aggressive large B cell lymphoma, the combination of mosunetuzumab and polatuzumab vedotin achieved a high overall response rate of 59.2% and a complete response rate of 45.9%, indicating strong efficacy as a second-line therapy.

The treatment demonstrated a favorable safety profile, with the most common serious side effects being neutropenia (25%) and fatigue (6.7%), and only 16.7% of patients experiencing any-grade cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Budde, LE., Olszewski, AJ., Assouline, S., et al.[2023]

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 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 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]

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 is an approved treatment for relapsed or refractory diffuse large B-cell lymphoma, specifically targeting the CD79b protein on B cells.

The drug works by delivering a cytotoxic molecule that inhibits tubulin polymerization, effectively killing the targeted cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin Approved for DLBCL. [2020]

References

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

A multicenter retrospective study of polatuzumab vedotin in patients with large B-cell lymphoma after CAR T-cell therapy. [2023]

2. 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]

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

Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. [2023]

4. 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]

5. 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]

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

Polatuzumab Vedotin: First Global Approval. [2023]

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

Mosunetuzumab: First Approval. [2022]

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

Polatuzumab Vedotin Approved for DLBCL. [2020]