Loncastuximab Tesirine for Non-Hodgkin's Lymphoma

Overseen By Paolo Strati, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: IV antimicrobials

Disqualifiers: Active infection, Cardiac disease, Autoimmune, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if loncastuximab tesirine (called "lonca" in this informed consent form) can help to control large B-cell lymphoma that is relapsed or refractory after receiving CAR T-cell therapy. The safety and possible effects of the study therapy will also be studied.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the study team to get a clear answer.

What data supports the effectiveness of the drug Loncastuximab Tesirine for treating Non-Hodgkin's Lymphoma?

Research shows that Loncastuximab Tesirine, a drug targeting CD19 on cancer cells, has been effective in treating relapsed or refractory diffuse large B-cell lymphoma, a type of Non-Hodgkin's Lymphoma. In clinical trials, it showed an overall response rate of about 48%, with some patients achieving complete remission, and it was approved by the FDA for this use due to its demonstrated safety and effectiveness. ^{1 2 3 4 5}

What safety data exists for CAR T-cell therapy, including Loncastuximab Tesirine, in humans?

CAR T-cell therapy, including treatments like Loncastuximab Tesirine, has shown promise in treating certain cancers but comes with potential safety concerns. Common side effects include cytokine release syndrome (a severe immune reaction) and neurological issues, which can be serious but are manageable with proper medical care. Other risks include infections, cardiac effects, and nonrelapse mortality, which require careful monitoring and management by healthcare professionals. ^{6 7 8 9 10}

How is loncastuximab tesirine different from other drugs for non-Hodgkin's lymphoma?

Loncastuximab tesirine is unique because it is an antibody-drug conjugate that specifically targets CD19, a protein found on B-cells, and delivers a powerful cancer-killing agent directly to these cells. This targeted approach can be more effective and potentially have fewer side effects compared to traditional chemotherapy, which affects both cancerous and healthy cells. ^{1 2 5 11 12}

Research Team

Paolo Strati

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with certain types of large B-cell lymphoma that didn't respond well to CAR T-cell therapy can join this trial. They should have partially responded to the previous treatment, be in good physical condition, and not have had any other cancer treatments since. People with heart issues, blood clots, severe allergies to study drugs, or active infections can't participate. Women who could get pregnant must test negative for pregnancy and agree to use birth control.

Inclusion Criteria

Baseline oxygen saturation greater than 92% on room air

Platelet count of 50×10^9/L or higher without transfusion for 3 days prior to screening assessment

My white blood cell count is healthy without needing medication for the last 3 days.

Exclusion Criteria

I have an autoimmune disease that has damaged my organs or needed strong medication in the last 2 years.

I have fluid buildup needing drainage or causing breathing issues.

I am currently pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Loncastuximab Tesirine (lonca) by vein as consolidation therapy

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• CAR T-cell Therapy
• Loncastuximab Tesirine

Trial Overview The trial is testing whether a drug called Loncastuximab Tesirine (lonca) can help control large B-cell lymphoma after CAR T-cell therapy has been given. It's for patients whose cancer hasn't fully responded and will look at how safe lonca is and what effects it might have.

Participant Groups

Group I: Loncastuximab Tesirine Experimental Treatment 1 Intervention

Participants will receive Loncastuximab Tesirine (lonca) by vein.

CAR T-cell Therapy is already approved in United States, European Union for the following indications:

Approved in United States as CAR T-cell Therapy for:

• Relapsed or refractory B-cell acute lymphoblastic leukemia
• Relapsed or refractory B-cell non-Hodgkin's lymphoma
• Relapsed or refractory mantle cell lymphoma
• Relapsed or refractory follicular lymphoma
• Relapsed or refractory multiple myeloma

Approved in European Union as CAR T-cell Therapy for:

• Relapsed or refractory B-cell acute lymphoblastic leukemia
• Relapsed or refractory B-cell non-Hodgkin's lymphoma
• Relapsed or refractory mantle cell lymphoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a phase 2 trial involving 145 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), loncastuximab tesirine demonstrated a significant overall response rate of 48.3%, indicating its effectiveness as a treatment option for this challenging patient population.

The treatment was associated with an acceptable safety profile, with serious adverse events occurring in 39% of patients, but none were directly linked to loncastuximab tesirine, suggesting it may be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Caimi, PF., Ai, W., Alderuccio, JP., et al.[2021]

In a study involving 80 patients from the LOTIS-2 trial, loncastuximab tesirine (Lonca) demonstrated a significantly higher overall response rate (53.4%) compared to chemoimmunotherapy (CIT) treatments (40.3%) for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).

Lonca also showed improved overall survival, with a median survival of 10.8 months compared to 6.4 months for CIT, indicating it may be a more effective treatment option for patients with R/R DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparison of the Efficacy of Loncastuximab Tesirine Versus Treatment in the Chemoimmunotherapy Era for Relapsed/Refractory Diffuse Large B-cell Lymphoma. Hamadani, M., Chen, L., Song, Y., et al.[2022]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody-drug conjugate, has shown a 48.3% overall response rate in patients with relapsed, refractory diffuse large B-cell lymphoma during the phase II LOTIS-2 trial, indicating its efficacy as a treatment option.

The drug demonstrated a tolerable safety profile with common side effects including neutropenia and thrombocytopenia, and no new safety concerns were identified in the phase II trial, suggesting it is safe for further testing in various non-Hodgkin lymphoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine for diffuse large B-cell lymphoma. Zurko, J., Hamadani, M.[2021]

In a phase 1 study involving 183 patients with relapsed or refractory B-cell non-Hodgkin lymphoma, loncastuximab tesirine demonstrated a promising overall response rate of 45.6%, with 26.7% achieving complete responses, indicating its potential as an effective treatment option.

The study established a recommended dose of 150 µg/kg for phase 2 trials, with an acceptable safety profile characterized by manageable hematologic toxicities, suggesting that loncastuximab tesirine could be a viable alternative to current therapies for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Hamadani, M., Radford, J., Carlo-Stella, C., et al.[2022]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody-drug conjugate, has shown a 48.6% overall response rate in patients with relapsed, refractory diffuse large B-cell lymphoma, indicating its efficacy as a treatment option.

The drug has a tolerable safety profile, with common side effects including neutropenia and thrombocytopenia, leading to its recent FDA approval for treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a review of clinical data. Furqan, F., Hamadani, M.[2022]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

CAR-T cell therapies targeting CD19 have shown the ability to induce long-lasting remissions and improve disease-free survival in patients with treatment-resistant B cell malignancies, highlighting their efficacy in specific cancer types.

Immune checkpoint inhibitors (ICIs) have also demonstrated the potential for durable remissions and extended survival in patients with melanoma, Hodgkin's lymphoma, and non-small cell lung cancer, although both CAR-T and ICI therapies can lead to significant toxicities, including fatalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of chimeric antigen receptor engineered T cell-based and immune checkpoint blockade-based cancer immunotherapies. Hegde, UP., Mukherji, B.[2019]

Cancer immunotherapy, including HER2-targeted therapies like trastuzumab, immune checkpoint inhibitors, and CAR-T cell therapy, has significantly improved cancer patient outcomes by harnessing the immune system to target and kill cancer cells.

While trastuzumab is effective for HER2-positive cancers, it can cause reversible left ventricular dysfunction, whereas immune checkpoint inhibitors and CAR-T therapy may lead to serious cardiac side effects, including myocarditis and cytokine release syndrome, which can be life-threatening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs. Montisci, A., Vietri, MT., Palmieri, V., et al.[2023]

In a study of 957 patients receiving CAR T-cell therapy for relapsed/refractory large B-cell lymphomas, the overall nonrelapse mortality (NRM) rate was 5.0%, with the majority of deaths occurring later than 28 days post-infusion, primarily due to infections.

Risk factors for increased NRM included diabetes and elevated ferritin levels at the time of lymphodepletion, which can help guide physicians in selecting and managing patients to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonrelapse mortality after CAR T-cell therapy for large B-cell lymphoma: a LYSA study from the DESCAR-T registry. Lemoine, J., Bachy, E., Cartron, G., et al.[2023]

Adoptive T cell therapy (ACT) is a promising and personalized cancer treatment that has shown significant effectiveness, particularly with TIL, TCR, and CAR-engineered T cells, leading to FDA approvals for certain B-cell malignancies.

Despite its potential, only a small percentage of patients with advanced cancers currently benefit from ACT due to treatment-related toxicities, highlighting the need for improved safety measures and an international consensus on toxicity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Adoptive Cell Therapy in Cancer. Wolf, B., Zimmermann, S., Arber, C., et al.[2022]

In a study of 35 adults with relapsed or refractory B-cell acute lymphoblastic leukemia, loncastuximab tesirine, an antibody-drug conjugate targeting CD19, showed promising preliminary clinical activity with 3 patients achieving complete responses at different doses.

The treatment was generally well-tolerated, with common side effects including nausea and febrile neutropenia, but no treatment-related deaths were reported, indicating a favorable safety profile despite a high incidence of grade ≥3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine, an anti-CD19 antibody-drug conjugate, in relapsed/refractory B-cell acute lymphoblastic leukemia. Jain, N., Stock, W., Zeidan, A., et al.[2023]

In a phase I study involving 88 patients with relapsed/refractory B-cell non-Hodgkin lymphoma, loncastuximab tesirine demonstrated a promising overall response rate of 59.4% at doses of 120 μg/kg or higher, with 40.6% achieving a complete response.

The treatment was associated with a high incidence of treatment-emergent adverse events (98.9%), primarily hematologic abnormalities and fatigue, but overall, it was considered to have acceptable safety, leading to the initiation of a phase II study at a starting dose of 150 μg/kg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Kahl, BS., Hamadani, M., Radford, J., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. [2021]

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

Matching-adjusted Indirect Comparison of the Efficacy of Loncastuximab Tesirine Versus Treatment in the Chemoimmunotherapy Era for Relapsed/Refractory Diffuse Large B-cell Lymphoma. [2022]

3. Spain pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine for diffuse large B-cell lymphoma. [2021]

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

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a review of clinical data. [2022]

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

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Current status of chimeric antigen receptor engineered T cell-based and immune checkpoint blockade-based cancer immunotherapies. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs. [2023]

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

Nonrelapse mortality after CAR T-cell therapy for large B-cell lymphoma: a LYSA study from the DESCAR-T registry. [2023]

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

Safety and Tolerability of Adoptive Cell Therapy in Cancer. [2022]

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

Loncastuximab tesirine, an anti-CD19 antibody-drug conjugate, in relapsed/refractory B-cell acute lymphoblastic leukemia. [2023]

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

A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. [2020]