Loncastuximab Tesirine + Mosunetuzumab for Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Steroids, Immunosuppressants, HAART, others

Disqualifiers: HIV, Hepatitis, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years post-last dose

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the safety and how well of loncastuximab tesirine when given together with mosunetuzumab works in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Loncastuximab tesirine is a monoclonal antibody, loncastuximab, linked to a toxic agent called tesirine. Loncastuximab attaches to anti-CD19 cancer cells in a targeted way and delivers tesirine to kill them. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving loncastuximab tesirine with mosunetuzumab may help treat patients with relapsed or refractory diffuse large B-cell lymphoma.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on systemic steroid therapy for lymphoma symptom control, it must be reduced to 20 mg/day prednisone or equivalent. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Loncastuximab Tesirine + Mosunetuzumab for lymphoma?

Loncastuximab Tesirine has shown effectiveness in treating relapsed or refractory diffuse large B-cell lymphoma, with a response rate of 48.3% in a clinical trial. Mosunetuzumab has been conditionally approved in the EU for relapsed or refractory follicular lymphoma, indicating its potential effectiveness in similar conditions. ^{1 2 3 4 5}

What is known about the safety of Loncastuximab Tesirine (Zynlonta) in humans?

Loncastuximab Tesirine, also known as Zynlonta, has been approved by the FDA for treating a type of lymphoma called diffuse large B-cell lymphoma. It is generally considered safe for use in humans, but like many treatments, it may have side effects, and its safety profile is based on its use in this specific condition. ^{6 7 8 9 10}

What makes the drug combination of Loncastuximab Tesirine and Mosunetuzumab unique for treating lymphoma?

This drug combination is unique because it combines Loncastuximab Tesirine, an antibody-drug conjugate targeting CD19 on B cells, with Mosunetuzumab, a bispecific antibody that engages T-cells to target CD20 on B cells, offering a novel approach by simultaneously targeting two different proteins on lymphoma cells. ^{1 2 3 11 12}

Research Team

Swetha Kambhampati

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

Adults (18+) with relapsed or refractory diffuse large B-cell lymphoma, including certain subtypes, who have had at least one prior therapy can join. Participants must be in good physical condition (ECOG <=2), not pregnant or breastfeeding, and willing to use birth control. They should not have active infections like HIV or hepatitis, autoimmune diseases needing treatment, recent major surgery unrelated to diagnosis, or a history of certain severe reactions to similar drugs.

Inclusion Criteria

I am a woman who can have children and my pregnancy test is negative.

Documented informed consent of the participant and/or legally authorized representative

My white blood cell count is healthy or can be with treatment.

Exclusion Criteria

Concomitant investigational therapy

I haven't had radiotherapy in the last 2 weeks.

I have had a solid organ transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-In

Evaluate the safety and tolerability of loncastuximab tesirine plus mosunetuzumab

Up to 30 days post-last dose

Multiple visits for IV administration and monitoring

Treatment

Patients receive loncastuximab tesirine and mosunetuzumab intravenously

Up to 2 years post-last dose

Regular visits for IV administration, PET/CT scans, and biopsies

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years post-last dose

Treatment Details

Interventions

• Loncastuximab Tesirine
• Mosunetuzumab

Trial Overview The trial is testing the combination of two drugs: Loncastuximab Tesirine and Mosunetuzumab for treating patients whose diffuse large B-cell lymphoma has returned after treatment or hasn't responded. The study will assess the safety and effectiveness of this drug duo.

Participant Groups

Group I: Treatment (oncastuximab tesirine, mosunetuzumab) Experimental Treatment 6 Interventions

Patients receive loncastuximab tesirine IV and mosunetuzumab IV on study. Patients also undergo PET/CT scan, biopsy, and collection of blood samples on study.

Loncastuximab Tesirine is already approved in United States, European Union for the following indications:

Approved in United States as Zynlonta for:

• Diffuse large B-cell lymphoma (DLBCL)
• DLBCL arising from low-grade lymphoma
• High-grade B-cell lymphoma

Approved in European Union as Zynlonta for:

• Diffuse large B-cell lymphoma (DLBCL)
• DLBCL arising from low-grade lymphoma
• High-grade B-cell lymphoma

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Loncastuximab tesirine is an antibody-drug conjugate that targets B cell lymphomas, specifically approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL) after two or more lines of treatment.

The drug works by using an anti-CD19 antibody to deliver a DNA-alkylating agent directly to B cells, enhancing its efficacy in targeting cancer cells while minimizing damage to healthy cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab Tesirine: First Approval. Lee, A.[2021]

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]

Mosunetuzumab, a bispecific antibody targeting CD20 and CD3, has received conditional approval in the EU for treating adults with relapsed or refractory follicular lymphoma after at least two prior therapies.

This approval marks a significant milestone in the development of mosunetuzumab, highlighting its potential as a new treatment option for patients with difficult-to-treat lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab: First Approval. Kang, C.[2022]

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]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody drug, has been safely administered at full doses to patients with relapsed/refractory DLBCL despite their severe hepatic dysfunction, suggesting potential efficacy in this challenging patient population.

The cases presented highlight the need for further investigation into the safety and dosing guidelines of loncastuximab tesirine-lpyl in patients with moderate to severe liver impairment, as current guidance from the manufacturer is unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of loncastuximab tesirine-lpyl in diffuse large B-cell lymphoma with severe hepatic dysfunction. Baek, GT., Huang, IJ., Gopal, AK.[2023]

Loncastuximab tesirine, an antibody-drug conjugate targeting CD19, has shown promising efficacy in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with overall response rates of 42.3% in LOTIS-1 and 48.3% in LOTIS-2 trials.

The treatment has an acceptable safety profile, with common side effects including anemia, neutropenia, fatigue, and nausea, making it a viable option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. Xu, B.[2022]

In a study involving 364 patients with systemic lupus erythematosus (SLE), long-term treatment with belimumab combined with standard therapy demonstrated a stable or declining incidence of adverse events over 4 years, indicating a favorable safety profile.

The most common side effects were mild, such as arthralgia and upper respiratory infections, and serious infusion reactions were rare, suggesting that belimumab can be safely administered for extended periods in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. Merrill, JT., Ginzler, EM., Wallace, DJ., et al.[2013]

In a study of 30 patients with recently diagnosed systemic lupus erythematosus (SLE) treated with belimumab for 6 months, significant improvements were observed in key laboratory markers, including increased white blood cell counts and hemoglobin levels, and decreased disease activity scores.

Belimumab was found to be safe and effective, potentially reducing the need for glucocorticoids and improving anemia, with minimal adverse reactions reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term clinical observations of belimumab in the treatment of recently diagnosed systemic lupus erythematosus. Wu, C., Gong, B.[2022]

Rituximab, a B cell-targeted biologic used for autoimmune diseases, has a low incidence of serious infections, but there is a rare risk of progressive multifocal leucoencephalopathy, occurring in about 5 out of 100,000 patients, with no proven causal link established.

Repeated use of rituximab can lead to hypogammaglobulinaemia, which increases the risk of serious infections, highlighting the need for careful monitoring of patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B Cell Therapies, Approved and Emerging: a Review of Infectious Risk and Prevention During Use. Md Yusof, MY., Vital, EM., Buch, MH.[2022]

In a study of 11 girls with severe childhood-onset systemic lupus erythematosus (SLE), rituximab treatment led to remission in 6 out of 8 patients with lupus nephritis and both patients with autoimmune cytopenia, indicating its potential efficacy as a co-therapy.

However, the study also reported that 45% of patients experienced severe adverse events, highlighting the need for caution and further research to better understand the safety profile of rituximab in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab therapy for childhood-onset systemic lupus erythematosus. Willems, M., Haddad, E., Niaudet, P., et al.[2015]

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]

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]

References

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

Loncastuximab Tesirine: First Approval. [2021]

2. Spain pubmed.ncbi.nlm.nih.gov

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

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

Mosunetuzumab: First Approval. [2022]

4. 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]

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

Safety of loncastuximab tesirine-lpyl in diffuse large B-cell lymphoma with severe hepatic dysfunction. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine: an effective therapy for relapsed or refractory diffuse large B-cell lymphoma. [2022]

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

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Short-term clinical observations of belimumab in the treatment of recently diagnosed systemic lupus erythematosus. [2022]

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

B Cell Therapies, Approved and Emerging: a Review of Infectious Risk and Prevention During Use. [2022]

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

Rituximab therapy for childhood-onset systemic lupus erythematosus. [2015]

11. 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]

12. 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]