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

Trial Summary

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.

What data supports the effectiveness of the treatment Axi-cel + Glofitamab for B-Cell Lymphoma?

Research shows that axicabtagene ciloleucel (axi-cel) has been effective in treating various types of B-cell lymphomas, including large B-cell lymphoma and follicular lymphoma, with high response rates and durable remissions. It has been approved by the FDA for certain types of lymphoma, demonstrating significant clinical benefits in trials. ^{1 2 3 4 5}

Is the Axi-cel + Glofitamab treatment safe for humans?

Axi-cel (Axicabtagene Ciloleucel) has been studied for B-cell lymphomas and shows a manageable safety profile, but common side effects include cytokine release syndrome (a severe immune reaction), neurological issues, infections, fever, diarrhea, nausea, low blood pressure, and fatigue. Glofitamab safety data is not provided in the articles, so consult with a healthcare provider for more information. ^{1 2 3 6 7}

How is the treatment Axi-cel + Glofitamab for B-Cell Lymphoma different from other treatments?

This treatment combines axicabtagene ciloleucel (axi-cel), a CAR T-cell therapy that targets CD19 on cancer cells, with glofitamab, a bispecific antibody that engages both cancer cells and immune cells, offering a novel approach to treating B-cell lymphoma. Axi-cel has shown high response rates and durable remissions in relapsed/refractory cases, making it a promising option for patients who have not responded to other treatments. ^{1 3 4 6 8}

What is the purpose of this trial?

To learn if the combination of axicabtagene ciloleucel (axi-cel) and glofitamab as first-line therapy in high-risk LBCL participants or as second-line therapy in LBCL participants can help to control the disease.

Research Team

Jason Westin

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

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) 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]

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) 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]

References

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

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. [2022]

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

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

3. United States 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. [2021]

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

Axicabtagene Ciloleucel in the Management of Follicular Lymphoma: Current Perspectives on Clinical Utility, Patient Selection and Reported Outcomes. [2023]

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

FDA Approval Summary: Axicabtagene Ciloleucel for Second-Line Treatment of Large B-Cell Lymphoma. [2023]

6. United States 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. [2022]

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

Three-Year Follow-Up Analysis of Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (ZUMA-5). [2023]