Axi-cel + Glofitamab for B-Cell Lymphoma

Overseen By Jason Westin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Anti-CD20 antibody, Anthracycline

Must not be taking: Aminoglycosides, Antiretrovirals

Disqualifiers: CNS disorder, Cardiovascular disease, Autoimmune 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: 6 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of two treatments, axi-cel (a type of CAR T-cell therapy) and glofitamab (a monoclonal antibody), can effectively manage B-Cell Lymphoma. It targets individuals whose cancer did not fully respond to their first treatment or returned within a year. Suitable candidates for this trial include those with this type of lymphoma, who have tried initial treatments that were ineffective or stopped working quickly, and who can attend required hospital visits. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a chance to benefit from innovative therapies.

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, at least 2 weeks must have passed since any prior systemic therapy before starting the trial.

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

Research has shown that axicabtagene ciloleucel (axi-cel) and glofitamab, studied separately, have promising safety results. Axi-cel, used for patients with large B-cell lymphoma, has a good safety record and has helped some patients live longer. Studies indicate it is generally well-tolerated, though some patients might experience side effects like fever or tiredness.

Glofitamab, another treatment for this type of lymphoma, has also demonstrated safe results. In patients who have undergone many previous treatments, it achieved a 46% overall response rate, with some experiencing a complete response. Side effects are usually manageable and can include fever or low blood cell counts.

Researchers are now testing these treatments together to determine if they work better as a combination. Since both have shown good safety individually, there is hope for their combined use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Axicabtagene Ciloleucel (axi-cel) and Glofitamab for treating B-cell lymphoma because of their unique mechanisms. Most current treatments focus on chemotherapy or targeted drugs like Rituximab. However, axi-cel is a CAR T-cell therapy that genetically modifies a patient's own immune cells to attack cancer cells, offering a personalized approach. Glofitamab, on the other hand, is a bispecific antibody that binds to both cancer cells and T-cells, enhancing the immune response. This combination aims to provide a more effective and targeted attack on lymphoma cells, potentially leading to better outcomes for patients.

What evidence suggests that the combination of axi-cel and glofitamab could be effective for B-cell lymphoma?

Studies have shown that axicabtagene ciloleucel (axi-cel) as a second-line treatment for large B-cell lymphoma can extend survival in patients whose disease returns or doesn't respond to initial treatments. This treatment helps patients live longer compared to some other options. In this trial, participants will receive a combination of axi-cel and glofitamab. Real-world data on treatments like axi-cel and glofitamab indicate that about 51.7% of patients respond, with 25.4% experiencing a complete response, meaning their cancer becomes undetectable. This combination aims to control the disease effectively, offering hope for better management of B-cell lymphoma. ^{1 2 4 6 7}

Who Is on the Research Team?

Jason Westin

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with Large B Cell Lymphoma who have already tried one treatment without success. Participants should be high-risk and looking to try a combination of two drugs, Axi-cel and Glofitamab, as either their first or second line of therapy.

Inclusion Criteria

My lymphoma is confirmed to be CD19 and CD20 positive.

My brain scans are clear of lymphoma after treatment.

I am of childbearing age and my pregnancy test is negative.

Exclusion Criteria

My lymphoma affects my heart.

I have a history of serious heart disease.

Primary immunodeficiency

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive axicabtagene ciloleucel (axi-cel) and glofitamab as combination therapy

6 months

Regular visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Periodic visits for safety and response assessment

Long-term follow-up

Participants are monitored for long-term safety and survival outcomes

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Axicabtagene Ciloleucel
• Glofitamab
• Obinutuzumab

Trial Overview The study tests if using Axicabtagene Ciloleucel (Axi-cel) together with Glofitamab can control the disease in those with relapsed or refractory Large B Cell Lymphoma. It's given after the first treatment fails or as an initial high-risk therapy.

How Is the Trial Designed?

Group I: Axicabtagene Ciloleucel (axi-cel) and Glofitamab Experimental Treatment 3 Interventions

Participants will receive glofitamab based on a step-up dosing regimen.

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

Approved in United States as Yescarta for:

• Large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy
• Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy
• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Approved in European Union as Yescarta for:

• Diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy
• Relapsed or refractory DLBCL and primary mediastinal large B-cell lymphoma, after two or more lines of systemic therapy
• Relapsed or refractory follicular lymphoma after three or more lines of systemic therapy

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

Kite, A Gilead Company

Industry Sponsor

Trials

45

Recruited

4,300+

Published Research Related to This Trial

In a study of 122 patients treated with axicabtagene ciloleucel (axi-cel) for relapsed aggressive B-cell non-Hodgkin lymphoma, the overall response rate was 70% and the complete response rate was 50%, indicating strong efficacy even in a post-commercial setting with relaxed eligibility criteria.

Patients eligible for the original ZUMA-1 trial had significantly better outcomes, including higher complete response rates (63% vs. 42%) and longer duration of response, progression-free survival, and overall survival, while the rates of severe side effects like cytokine release syndrome and neurotoxicity were consistent with those observed in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. Jacobson, CA., Hunter, BD., Redd, R., et al.[2022]

Axicabtagene ciloleucel (axi-cel) demonstrated impressive efficacy in treating relapsed/refractory large B-cell lymphoma, with overall and complete response rates of 83% and 58%, respectively, in the pivotal ZUMA-1 trial with a median follow-up of 27.1 months.

While axi-cel shows promise, it is associated with significant toxicities, including cytokine release syndrome (CRS) in 7% to 14% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 31% to 55%, highlighting the need for careful patient management and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma. Halford, Z., Anderson, MK., Bennett, LL.[2021]

In a retrospective study of 275 patients with relapsed/refractory large B-cell lymphoma (LBCL) receiving axicabtagene ciloleucel (axi-cel), the overall response rate was 82% and the complete response rate was 64%, demonstrating strong efficacy similar to the original ZUMA-1 trial.

Safety profiles showed that 7% of patients experienced severe cytokine release syndrome and 31% had neurotoxicity, with a nonrelapse mortality rate of 4.4%, indicating manageable risks associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. Nastoupil, LJ., Jain, MD., Feng, L., et al.[2022]

Yescarta (axicabtagene ciloleucel) is an engineered T-cell therapy that showed a 66% overall response rate and a 47% complete response rate in treating relapsed or refractory diffuse large B-cell lymphoma, based on a phase II study with a median follow-up of 15.1 months.

The therapy was associated with manageable adverse events, including cytokine release syndrome and neurological issues, making it a promising option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. Papadouli, I., Mueller-Berghaus, J., Beuneu, C., et al.[2022]

Axicabtagene ciloleucel (axi-cel) was approved by the FDA for adults with large B-cell lymphoma (LBCL) that does not respond to initial treatment or relapses within 12 months, based on the ZUMA-7 trial involving 359 patients, which showed significantly longer event-free survival compared to standard therapy (8.3 months vs. 2.0 months).

While axi-cel demonstrated high efficacy, it was associated with notable side effects, including cytokine release syndrome in 92% of patients and neurologic toxicity in 74%, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Axicabtagene Ciloleucel for Second-Line Treatment of Large B-Cell Lymphoma. Sharma, P., Kasamon, YL., Lin, X., et al.[2023]

The interim analysis of the phase 2 ZUMA-5 study showed that axicabtagene ciloleucel (axicel; Yescarta) provided significant and durable clinical benefits for patients with relapsed or refractory indolent non-Hodgkin lymphoma, indicating its efficacy in this patient population.

The treatment demonstrated a high overall response rate (ORR) and complete response (CR) rate, while maintaining a manageable safety profile, suggesting it is a viable option for patients with this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim Phase 2 ZUMA-5 Results Show Promise for Axi-Cel in R/R iNHL. Slater, H.[2021]

Axicabtagene ciloleucel (axi-cel) is an effective CAR-T therapy for relapsed/refractory follicular lymphoma, demonstrating high response rates and durable remissions in patients with challenging disease characteristics.

The ZUMA-5 study indicates that axi-cel has manageable toxicities and should be considered a standard treatment option for patients with relapsed/refractory follicular lymphoma beyond second-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel in the Management of Follicular Lymphoma: Current Perspectives on Clinical Utility, Patient Selection and Reported Outcomes. Mohty, R., Kharfan-Dabaja, MA., Chavez, JC.[2023]

Axicabtagene ciloleucel (axi-cel) is an effective CAR T-cell therapy for relapsed/refractory follicular lymphoma, showing a high overall response rate of 94% after a median follow-up of 41.7 months in the ZUMA-5 study with 127 patients.

The therapy demonstrated durable responses with a median progression-free survival of 40.2 months and very few relapses beyond 2 years, indicating long-term efficacy and manageable safety in patients with relapsed indolent non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Follow-Up Analysis of Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (ZUMA-5). Neelapu, SS., Chavez, JC., Sehgal, AR., 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 ... Key PointsBispecifics had an ORR and CR rate of 51.7% and 25.4%, respectively; median PFS and OS were 2.5 and 7.8 months, respectively.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2301665

Survival with Axicabtagene Ciloleucel in Large B-Cell ... Axi-cel as second-line treatment for patients with early relapsed or refractory large B-cell lymphoma resulted in significantly longer overall survival than ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7023

Trends and outcomes by inpatient and outpatient infusion ... Here, we present safety and effectiveness outcomes of axi-cel by intention to treat in OPT and IPT settings in a multicenter real-world dataset.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723022479

A Cost-Effectiveness Analysis of Axicabtagene Ciloleucel ... This simulation suggests that axi-cel is cost effective compared to glofitamab in a 3L DLBCL setting based on extrapolation of the pivotal trial data.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06213311

NCT06213311 | A Study of Axicabtagene Ciloleucel and ... A Study of Axicabtagene Ciloleucel and Glofitamab as Second-Line Therapy for Relapsed or Refractory Patients With Large B Cell Lymphoma · Study Overview.

6. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3865/534578/Safety-and-efficacy-of-glofitamab-for-relapsed

Safety and efficacy of glofitamab for relapsed/refractory large ... Glofitamab has a 46% ORR (27% CR; 19% PR) and a manageable safety in heavily pretreated patients with r/r LBCL.

7. 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% ...