Combination Therapy for Non-Hodgkin's Lymphoma

Not currently recruiting at 41 trial locations

Overseen By Reference Study ID Number: NP39488 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Corticosteroids, Immunosuppressives, Chemotherapy, others

Disqualifiers: CLL, CNS disease, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: 12-24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of medicines to treat non-Hodgkin's lymphoma, aiming to find the best dose and understand the treatment's mechanism and safety. Participants will receive a mix of drugs, including atezolizumab (Tecentriq), glofitamab (COLUMVI or glofitamab-gxbm), and polatuzumab vedotin (Polivy), to determine if this combination can control the cancer. Individuals with certain types of lymphoma that have not responded to previous treatments or have recurred may be suitable candidates. A sub-study uses imaging to observe how a specific type of immune cell reacts before and after treatment. This study excludes those with certain other health conditions or treatments, such as chronic lymphocytic leukemia or recent major surgery. As a Phase 1, Phase 2 trial, it focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you stop taking any standard anti-cancer treatments, including investigational therapies, within 4 weeks before starting the study treatment. If you are on corticosteroids, you must not exceed 25 milligrams per day of prednisone or its equivalent within 4 weeks before and during the study.

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

Research has shown that combining atezolizumab and glofitamab is promising in terms of safety. Atezolizumab, when used with other treatments, was well-tolerated and led to good outcomes in patients with certain types of lymphoma. Glofitamab has demonstrated a safety profile manageable for patients with aggressive non-Hodgkin's lymphoma.

Studies suggest that the combination of polatuzumab vedotin and glofitamab is generally safe and effective for patients with lymphoma that has returned or not responded to other treatments. Patients have found this combination manageable even after other treatments have failed.

Both treatment combinations are in early testing stages, so researchers are still determining the best doses and closely monitoring safety. However, current data is encouraging, showing that both combinations can be tolerated by patients. Always consult your healthcare provider to determine if a clinical trial is right for you. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Non-Hodgkin's Lymphoma because they introduce innovative mechanisms and combinations that differ from standard chemotherapy or radiation. Atezolizumab is an immunotherapy that works by unleashing the immune system to attack cancer cells, a method distinct from traditional treatments. Glofitamab is a bispecific antibody that targets two different proteins on cancer cells, potentially enhancing precision in attacking the tumor. Polatuzumab Vedotin combines an antibody with chemotherapy, delivering the drug directly to the cancer cells, which may reduce side effects compared to conventional chemotherapy. Together, these treatments represent a cutting-edge approach that could improve outcomes and minimize adverse effects for patients.

What evidence suggests that this trial's combination treatments could be effective for non-Hodgkin's lymphoma?

Research has shown that combining atezolizumab with glofitamab, one of the treatment arms in this trial, yields promising results for patients with relapsed or hard-to-treat diffuse large B-cell lymphoma, a type of non-Hodgkin's lymphoma. In earlier studies, patients who received this combination lived longer, with 87.9% remaining disease-free after two years and 96.3% still alive.

Another treatment arm in this trial combines glofitamab with polatuzumab vedotin. This combination has proven very effective for patients who have undergone multiple treatments for relapsed or hard-to-treat large B-cell lymphoma. Studies indicate that this combination leads to long-lasting treatment effects. These findings suggest that both treatment combinations in this trial offer hope for patients with challenging forms of non-Hodgkin's lymphoma. ^{1 4 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

Adults with B-cell Non-Hodgkin's Lymphoma that has come back or didn't respond to treatment, and who have no other life-prolonging therapy options. Participants must have at least one measurable lesion, be in relatively good health (ECOG 0-2), and have proper organ function. They can't join if they've had certain autoimmune diseases, lung conditions, recent cancer treatments, transplants, infections or vaccinations.

Inclusion Criteria

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

My liver, blood, and kidney functions are all within normal ranges.

Negative test results for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV)

Exclusion Criteria

I do not have severe nerve damage in my hands or feet.

I have had lung conditions like pulmonary fibrosis or pneumonia, or my CT scan shows active lung inflammation.

I have had a stem cell transplant from a donor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Glofitamab in combination with Atezolizumab or Polatuzumab Vedotin up to the maximum tolerated dose (MTD)

12-24 weeks

Weekly visits (in-person)

Imaging Sub-study

Participants undergo PET/CT imaging to assess CD8+ T-cells at baseline and after treatment

1 cycle

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Monthly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Glofitamab
• Polatuzumab Vedotin

Trial Overview The trial is testing a combination of drugs including Glofitamab and Atezolizumab or Polatuzumab Vedotin for safety and effectiveness in treating lymphoma. It aims to find the highest dose patients can take without serious side effects (MTD) and suggests a Phase II dose (RP2D). There's also a sub-study using an imaging tracer to see how T-cells are affected by the treatment.

How Is the Trial Designed?

Group I: Polatuzumab Vedotin Experimental Treatment 4 Interventions

Participants will receive Glofitamab in combination with polatuzumab vedotin up to the MTD.

Group II: Imaging Sub-study Experimental Treatment 3 Interventions

Participants will undergo positive-emission tomography/computed tomography (PET/CT) at screening, followed by an "Imaging Cycle," to replace Cycle 1 of the main study. Eligible participants will have the option roll-over to the atezolizumab arm of the main study from Cycle 2 onwards.

Group III: Atezolizumab Experimental Treatment 4 Interventions

Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD).

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

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

Polatuzumab vedotin (PV) is an innovative antibody-drug conjugate that has been approved by the US FDA for treating refractory/relapsed diffuse large B-cell lymphoma, particularly in patients who are not eligible for stem cell transplants.

In a pivotal Phase II trial, PV demonstrated significant efficacy and an acceptable safety profile when used in combination with bendamustine and rituximab, highlighting its potential as a valuable treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin, an anti-CD79b antibody-drug conjugate for the treatment of relapsed/refractory diffuse large B-cell lymphoma. Camus, V., Tilly, H.[2021]

Glofitamab, a bispecific antibody, demonstrated a 53.8% overall response rate in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, with a complete response rate of 36.8%, indicating its efficacy in a heavily pretreated population.

The treatment had a manageable safety profile, with cytokine release syndrome occurring in 50.3% of patients but mostly at lower grades, and only 2.9% of patients withdrew due to adverse events, suggesting that glofitamab can be safely administered with prior obinutuzumab pretreatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. Hutchings, M., Morschhauser, F., Iacoboni, G., et al.[2023]

Rituximab, an anti-CD20 antibody, has been shown to be effective in treating various B-cell lymphoid malignancies, with benefits including improved response rates and progression-free survival, based on extensive clinical data since its introduction in 1997.

The drug is generally well-tolerated, with infusion-related side effects being the most significant, and its use has expanded from treating relapsed low-grade lymphomas to first-line therapy and more aggressive forms like diffuse large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab and its role as maintenance therapy in non-Hodgkin lymphoma. Collins-Burow, B., Santos, ES.[2015]

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]

Recent advances in targeted therapies for non-Hodgkin lymphoma, particularly the anti-CD20 monoclonal antibody rituximab, are expected to significantly improve patient care by inhibiting specific disease pathways.

Combining rituximab with other agents, such as monoclonal antibodies, immunomodulatory drugs, and Bcl-2 inhibitors, shows promise for enhancing treatment efficacy, especially in patients who do not respond to rituximab alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapies for non-Hodgkin lymphoma: rationally designed combinations. Martin, P., Leonard, JP.[2019]

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]

In a study of 7 patients with primary cutaneous B-cell lymphoma who had relapsed after chemotherapy, the combination of intravenous rituximab and single-dose cyclophosphamide resulted in an impressive overall response rate of 85.7%, with 5 patients achieving complete remission.

The treatment was well tolerated, and after a median follow-up of 13 months, most patients remained disease-free for significant durations, indicating promising efficacy and safety for this approach in managing relapsed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy with cyclophosphamide and anti-CD20 antibody (rituximab) in relapsed primary cutaneous B-cell lymphoma: a report of 7 cases. Fierro, MT., Savoia, P., Quaglino, P., et al.[2019]

Glofitamab, a bispecific monoclonal antibody targeting CD20 and CD3, was conditionally approved in Canada on March 25, 2023, for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who have undergone multiple prior therapies and are ineligible for CAR T-cell therapy.

The drug is currently under regulatory review in the EU and USA, with ongoing clinical development as both a standalone treatment and in combination with other therapies for non-Hodgkin lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab: First Approval. Shirley, M.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03533283

Study Details | NCT03533283 | An Open-Label Phase lB/II ... Participants will receive Glofitamab in combination with Atezolizumab up to the maximum tolerated dose (MTD). Intervention/Treatment, Drug : Glofitamab.

2. forpatients.roche.com forpatients.roche.com/content/patient-platform/global/en/trials/cancer/non-hodgkins-lymphoma/an-open-label-phase-lb-study-of-ro7082859-and-atezolizumab-in-ad.pdf

Cell Non-Hodgkin's Lymphoma - ForPatients New treatment combinations, such as glofitamab with atezolizumab or polatuzumab vedotin, could help people with relapsed or refractory. (R/R) B-cell NHL to live ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694104/

Atezolizumab combined with immunogenic salvage ... R-GemOx+Atezo was well tolerated and demonstrated promising preliminary efficacy in patients with relapsed/refractory transformed DLBCL. Introduction. Patients ...

4. ashpublications.org ashpublications.org/bloodadvances/article/9/14/3530/536801/Atezolizumab-consolidation-in-patients-with-high

Atezolizumab consolidation in patients with high-risk diffuse ... Atezolizumab consolidation in high-risk patients with DLBCL raised 2-year DFS to 87.9% and OS to 96.3%, surpassing historical outcomes.

5. clin.larvol.com clin.larvol.com/trial-detail/NCT03533283

An Open-Label Phase lB/II Study of Glofitamab and ... P1b/2 | N=211 | NCT03533283 | Sponsor: Hoffmann-La Roche | "Updated data from the Phase I/Ib investigational NP39488 study showed high and durable response ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12274673/

Atezolizumab consolidation in patients with high-risk diffuse ... Atezolizumab consolidation in high-risk patients with DLBCL raised 2-year DFS to 87.9% and OS to 96.3%, surpassing historical outcomes.

7. genentech-medinfo.com genentech-medinfo.com/our-products/oncology/columvi.html

Columvi® (glofitamab-gxbm) | Genentech Prescribing & ... Safety Data Sheets (MSDS) ... 20220208 Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/761309Orig1s000MultidisciplineR.pdf

761309Orig1s000 - accessdata.fda.gov ... safety data available allow for a comprehensive assessment of the safety profile of glofitamab ... non-Hodgkin's lymphoma, aNHL=aggressive non-Hodgkin's lymphoma,.