Combination Therapy for Non-Hodgkin's Lymphoma

Recruiting at 36 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

211 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination therapy for Non-Hodgkin's Lymphoma?

The research highlights that combining targeted therapies, like monoclonal antibodies, can be very effective in treating Non-Hodgkin's Lymphoma. Although specific data on the combination of Atezolizumab, Tecentriq, Glofitamab, COLUMVI, glofitamab-gxbm, Polatuzumab Vedotin, and Polivy is not provided, similar combinations with rituximab have shown significant effects, suggesting potential effectiveness. ^{1 2 3 4 5}

Is the combination therapy for Non-Hodgkin's Lymphoma safe?

Polatuzumab vedotin, part of the combination therapy, has shown an acceptable safety profile in clinical trials for relapsed or refractory large B-cell lymphomas, with manageable side effects. The risk of immune reactions is low, and the treatment has been used safely in various settings, including after other therapies like CAR T-cell therapy. ^{6 7 8 9 10}

What makes the combination therapy for Non-Hodgkin's Lymphoma unique?

This combination therapy is unique because it includes Glofitamab, a bispecific antibody that engages T-cells to target and destroy lymphoma cells, and Polatuzumab Vedotin, which delivers a toxic agent directly to cancer cells. This approach is different from traditional chemotherapy and aims to enhance the immune system's ability to fight the cancer. ^{1 4 11 12 13}

What is the purpose of this trial?

This is an open-label, single arm, multicenter, dose finding, Phase Ib study in order to assess the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) for this combination treatment and to evaluate the general safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and preliminary anti-tumor activity of this combination treatment in adult patients. This study includes an additional open-label imaging feasibility sub-study using a tracer in adult participants with relpased/refractory B-cell non-Hodgkin's lymphoma to image CD8+T-cells at baseline and after treatment with glofitamab, including pre-treatment with obinutuzumab.

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

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

Targeted therapies for non-Hodgkin lymphoma: rationally designed combinations. [2019]

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

Rituximab therapy of B-cell neoplasms. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Rituximab and its role as maintenance therapy in non-Hodgkin lymphoma. [2015]

4. United States 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. [2019]

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

Improving therapeutic activity of anti-CD20 antibody therapy through immunomodulation in lymphoid malignancies. [2019]

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

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

7. United States 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. [2023]

8. India pubmed.ncbi.nlm.nih.gov

Salvage Using Polatuzumab Vedotin Based Therapy in Relapsed Refractory Large B-Cell Lymphomas: Early Experience from a Real-World Middle-Income Setting Using Named-Patient Compassionate Access Program. [2023]

9. 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]

10. 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]

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

Durable complete responses from therapy with combined epratuzumab and rituximab: final results from an international multicenter, phase 2 study in recurrent, indolent, non-Hodgkin lymphoma. [2017]

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

Beyond rituximab: The future of monoclonal antibodies in B-cell non-Hodgkin lymphoma. [2021]

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

Glofitamab: First Approval. [2023]