Combination Therapy for Non-Hodgkin's Lymphoma

(MAPtivate-6 Trial)

Not currently recruiting at 31 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Pfizer

Must not be taking: Anti-CD47, Glofitamab

Disqualifiers: High grade B-cell lymphoma, others

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

Compensation: Varies

Number of Visits: 4

Duration: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of medicines for people with diffuse large B-cell lymphoma (DLBCL), a type of non-Hodgkin's lymphoma that has returned after treatment or hasn’t responded to previous treatments. The goal is to test the safety and effectiveness of these medicines when given together. Participants will receive a series of medicines through an IV, starting with obinutuzumab, followed by maplirpacept (an experimental treatment), and then glofitamab. People who have had DLBCL, tried at least two other treatments, and aren't interested in stem cell or CAR-T cell therapies might be a good fit for this study. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that glofitamab is generally well-tolerated, but some risks exist. In earlier studies, a small percentage of patients experienced serious infections, such as COVID-19 and sepsis, affecting about 6% and 4.1% of patients, respectively.

Early results suggest that maplirpacept (PF-07901801) is relatively safe when used with other treatments. However, ongoing studies mean that not all safety information is available yet.

Obinutuzumab has been used in other treatments, and safety data indicate it can cause side effects like infections and blood-related issues. Serious side effects, such as low white blood cell count (neutropenia) and pneumonia, have been reported in a significant number of cases.

In summary, while each of these medicines has its own safety considerations, various studies have used them with manageable risks. Participants should be aware of these potential side effects and discuss any concerns with their healthcare provider. ^{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 offer new ways to tackle the disease. Unlike traditional therapies that mostly focus on chemotherapy or the CD20 protein, these investigational treatments target different aspects of the cancer cells. Glofitamab is a bispecific antibody that links cancer cells to immune cells, prompting the immune system to attack the cancer. Maplirpacept (PF-07901801) introduces a novel molecule designed to fine-tune immune responses to fight cancer more effectively. Lastly, Obinutuzumab is an engineered antibody that enhances the immune system's ability to destroy cancer cells. Together, they promise a more comprehensive approach to treating Non-Hodgkin's Lymphoma, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for diffuse large B-cell lymphoma?

Research has shown that glofitamab, one of the treatments in this trial, yields promising results for people with diffuse large B-cell lymphoma (DLBCL). Studies found that more than half of the patients experienced a reduction in cancer, with a 52% overall response rate. Obinutuzumab, another drug in this trial, has effectively treated non-Hodgkin B cell lymphoma, with response rates reaching as high as 93.8% in some cases. Meanwhile, maplirpacept (PF-07901801), also part of this trial, is designed to help the immune system better target and destroy cancer cells. Early studies show it improves the process that allows immune cells to attack cancer cells. Although maplirpacept remains under investigation, its unique action offers hope for better cancer control. ^{6 7 8 9 10}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

Adults with a confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) that has returned or hasn't responded to treatment, who have tried at least one therapy including an anti-CD20 antibody but can't or won't get stem cell or CAR-T cell therapy. They should be in good enough health as measured by specific medical standards.

Inclusion Criteria

I've had 1-2 treatments for my condition, including one with an anti-CD20 antibody.

My liver, kidneys, and bone marrow are functioning well.

I can take care of myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

I currently have an active infection.

I have been treated with anti-CD47, glofitamab, or anti-CD20 x CD3 drugs and did not respond to obinutuzumab alone.

I had a stem cell transplant less than 12 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment

Participants receive a single dose of obinutuzumab followed by two step-up doses of glofitamab

1 week

1 visit (in-person)

Treatment

Participants receive maplirpacept (PF-07901801) weekly for the first three cycles and then every three weeks, and glofitamab every 3 weeks for approximately 9 months

9 months

Weekly visits for the first 3 cycles, then every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Glofitamab
• Maplirpacept (PF-07901801)
• Obinutuzumab

Trial Overview The trial is testing the combination of two drugs, maplirpacept and glofitamab, after an initial dose of obinutuzumab for relapsed/refractory DLBCL. Participants will receive these medications through IV infusions over several cycles to determine the safest and most effective dosage.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 3 Interventions

Participants will be randomized to 1 of 3 different dose levels of PF-07901801 which will be administered in combination with fixed doses of glofitamab after a dose of obinutuzumab. Approximately 50 participants will be enrolled.

Group II: Phase 1b Experimental Treatment 3 Interventions

Participants will be allocated to sequential dose levels of PF-07901801, administered in combination with fixed doses of glofitamab after a dose of obinutuzumab, to select doses of PF-07901801 for further evaluation in Phase 2. Approximately 20 participants will be enrolled.

Glofitamab is already approved in United States for the following indications:

Approved in United States as COLUMVI for:

• Relapsed or refractory diffuse large B-cell lymphoma not otherwise specified (DLBCL), or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Hoffmann-La Roche

Industry 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

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]

In a real-world study of 43 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) treated with glofitamab, the median overall survival was 8.8 months, indicating promising efficacy in a heavily pretreated population.

However, the study also highlighted significant safety concerns, with treatment-related deaths occurring due to cytokine release syndrome and febrile neutropenia, emphasizing the need for careful monitoring of hematological toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data. Birtas Atesoglu, E., Gulbas, Z., Uzay, A., et al.[2023]

Glofitamab is a novel bispecific T-cell recruiting antibody that targets both CD20 on B-cells and CD3 on T-cells, showing over 50% complete response rates in heavily treated patients with aggressive and indolent B-cell lymphoma during Phase 1 trials.

The unique 2:1 configuration of glofitamab allows for an extended half-life and superior binding to CD20, making it a promising option for patients with limited treatment choices, with ongoing trials evaluating its efficacy in combination therapies and earlier treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab CD20-TCB bispecific antibody. Minson, A., Dickinson, M.[2022]

Glofitamab, a bispecific antibody targeting CD20 and CD3, demonstrated clinical activity in patients with relapsed/refractory B-cell non-Hodgkin lymphoma during a phase 1 trial, showing T-cell activation and tumor cell killing.

The study identified that tumor intrinsic factors, such as TP53 signaling, may contribute to resistance against glofitamab, indicating that these factors could serve as important biomarkers for predicting treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamics and molecular correlates of response to glofitamab in relapsed/refractory non-Hodgkin lymphoma. Bröske, AE., Korfi, K., Belousov, A., et al.[2022]

Glofitamab is a promising new treatment for B cell lymphomas that do not respond to standard R-CHOP chemotherapy, which fails in over one-third of cases.

As a bispecific antibody targeting CD20 and CD3, glofitamab works by engaging T cells to attack tumor cells, offering a novel approach for patients with relapsed or refractory lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glofitamab therapy for diffuse large B cell lymphoma: latest updates from the 2022 ASH Annual Meeting. Wang, C., Liu, Y.[2023]

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 analyzing overall survival (OS) for five treatments of relapsed-refractory diffuse large B-cell lymphoma (DLBCL), tafasitamab plus lenalidomide showed the best OS with a median of 26.5 months and a hazard ratio of 0.514 compared to glofitamab, indicating it may be a more effective option.

Despite glofitamab's advanced mechanism as a bispecific antibody, it did not demonstrate a significant OS advantage over the other treatments, with a median survival of 11.7 months, suggesting that other therapies may be more beneficial for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatments for Relapsed-Refractory Diffuse Large B-cell Lymphoma: A Preliminary Evaluation of the Place in Therapy of Glofitamab, a Bispecific Monoclonal Antibody. Messori, A., Rivano, M., Mengato, D., et al.[2023]

Citations

1. ashpublications.org ashpublications.org/blood/article/146/18/2177/546196/Real-world-outcomes-of-patients-with-aggressive-B

Real-world outcomes of patients with aggressive B-cell ... For those treated with glofitamab, an estimated 70.0% of complete responders remained in response at 6 months; the proportion of partial ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12334432/

Efficacy and safety of Glofitamab in patients with R/R ... Glofitamab, a CD20-directed CD3 T-cell engager, was recently FDA-approved after demonstrating a 52% overall response rate (ORR) and a 39% ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206913

Glofitamab for Relapsed or Refractory Diffuse Large B-Cell ... Glofitamab therapy was effective for DLBCL. More than half the patients had an adverse event of grade 3 or 4.

4. oncologynewscentral.com oncologynewscentral.com/drugs/info/fda-rejects-glofitamab-for-diffuse-large-b-cell-lymphoma-indication

FDA Rejects Glofitamab for Diffuse Large B-cell Lymphoma ... Results from the trial showed a 41% reduction in the risk for death (hazard ratio, 0.59; 95% confidence interval, 0.40–0.89; P=.011) for ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.7519

Glofitamab step-up dosing (SUD): Complete response ... Updated data for glofitamab monotherapy SUD show higher preliminary response rates than previously reported in pts with R/R NHL who have failed multiple lines ...

6. columvi-hcp.com columvi-hcp.com/safety/important-safety-information.html

COLUMVI™ (glofitamab-gxbm) Important Safety Information Grade 3 or higher infections reported in ≥ 2% patients were COVID-19 infection (6%), including COVID-19 pneumonia, and sepsis (4.1%). Febrile neutropenia ...

7. columvi.com columvi.com/

COLUMVI (glofitamab-gxbm) is for people with certain types of ... It is not known if COLUMVI is safe and effective in children. The conditional approval of COLUMVI is based on response rate and durability of response.

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,.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05169515

NCT05169515 | A Study Evaluating the Safety, ... This study will evaluate the safety, efficacy, and pharmacokinetics of mosunetuzumab or glofitamab in combination with CELMoDs (CC-220 and/or CC-99282) in ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924007195

Safety and efficacy of glofitamab for relapsed/refractory ... Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) ...