Loncastuximab Tesirine Combinations for Non-Hodgkin's Lymphoma

Recruiting at 39 trial locations

Overseen By Contact ADC Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ADC Therapeutics S.A.

Must not be taking: Immunosuppressants, Corticosteroids, Antivirals, others

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

Compensation: Varies

Number of Visits: 34

Duration: Up to 1 year

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The primary objective of this study is to characterize the safety and tolerability of loncastuximab tesirine in combination with polatuzumab vedotin, glofitamab, or mosunetuzumab, and to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) for the combinations.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have had certain treatments recently, like chemotherapy or immunosuppressive medication, within a specific time before starting the study. It's best to discuss your current medications with the study team to get a clear answer.

Is Loncastuximab Tesirine safe for humans?

Loncastuximab Tesirine has been shown to have a tolerable safety profile in clinical trials for relapsed or refractory diffuse large B-cell lymphoma, with common side effects including low white blood cell counts, low platelet counts, and elevated liver enzymes. These side effects were generally manageable, and the treatment was approved by the US FDA based on its safety and efficacy. ^{1 2 3 4 5}

What makes the drug Loncastuximab Tesirine unique for treating non-Hodgkin's lymphoma?

Loncastuximab Tesirine is unique because it is an antibody-drug conjugate that specifically targets CD19 on B cells, delivering a potent toxin directly to cancer cells, which may offer a new option for patients with relapsed or refractory non-Hodgkin's lymphoma who have limited treatment choices. ^{2 6 7 8 9}

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

Loncastuximab Tesirine has shown effectiveness in treating relapsed or refractory diffuse large B-cell lymphoma, with an overall response rate of 48.3% in a phase II trial. Additionally, Glofitamab, another component of the combination, has been evaluated for its survival benefits in similar conditions, although it did not show a significant advantage over other treatments. ^{1 2 3 9 10}

Are You a Good Fit for This Trial?

Adults with relapsed or refractory B-cell non-Hodgkin Lymphoma who've had at least two prior treatments can join this trial. They must have measurable disease, adequate organ function, and agree to use effective contraception. Exclusions include significant health issues, recent other cancer therapies, live vaccines, certain infections like HIV/HBV/HCV, CNS lymphoma involvement, known drug hypersensitivities.

Inclusion Criteria

BL (for Arm C only)

I can provide a tissue sample from my tumor.

My B-cell non-Hodgkin Lymphoma has come back or didn't respond to treatment, and I've tried at least two treatments.

Exclusion Criteria

I have chronic hepatitis B and can't or won't take standard antiviral therapy.

History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH)

Breastfeeding or pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive loncastuximab tesirine in combination with other anti-cancer agents in 21-day cycles

Up to 1 year

Every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Approximately every 12 weeks (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Glofitamab
• Lenalidomide
• Loncastuximab Tesirine
• Mosunetuzumab
• Polatuzumab Vedotin
• Umbralisib

Trial Overview The study tests the safety and anti-cancer effects of Loncastuximab Tesirine combined with Polatuzumab Vedotin, Glofitamab or Mosunetuzumab in patients. It aims to find the highest dose patients can tolerate without severe side effects (MTD) and suggest a dose for further trials (RDE).

How Is the Trial Designed?

Group I: Part 2 (Dose Expansion): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C) Experimental Treatment 2 Interventions

Participants with B-NHL will receive loncastuximab tesirine in combination with polatuzumab vedotin at the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) if favorable results of Part 1 are received.

Group II: Part 2 (Dose Expansion): Loncastuximab Tesirine + Mosunetuzumab (Arm F) Experimental Treatment 2 Interventions

Participants with B-NHL will receive loncastuximab tesirine in combination with mosunetuzumab at the MTD and/or RDE if favorable results of Part 1 are received.

Group III: Part 2 (Dose Expansion): Loncastuximab Tesirine + Glofitamab (Arm E) Experimental Treatment 3 Interventions

Participants with B-NHL will receive loncastuximab tesirine in combination with glofitamab at the MTD and/or RDE if favorable results of Part 1 are received. In addition participants will receive obinutuzumab pre-treatment 1000 mg on C1 D1.

Group IV: Part 1 (Dose Escalation): Loncastuximab Tesirine + Polatuzumab Vedotin (Arm C) Experimental Treatment 2 Interventions

Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on Day (D) 1 of each cycle (where each cycle is 21 days). Participants will also receive polatuzumab vedotin at a dose of 1.8 mg/kg on D1 of each cycle, infusion will be started one hour after end of loncastuximab tesirine infusion.

Group V: Part 1 (Dose Escalation): Loncastuximab Tesirine + Mosunetuzumab (Arm F) Experimental Treatment 2 Interventions

Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on Day (D) 1 of each cycle (where each cycle is 21 days). Participants will also receive mosunetuzumab 5 mg on C1 D1, 45 mg for C1 D8, C1 D15 and cycles 2-8 D1.

Group VI: Part 1 (Dose Escalation): Loncastuximab Tesirine + Glofitamab (Arm E) Experimental Treatment 3 Interventions

Participants will receive escalating doses (90 µg/kg to 150 µg/kg) of loncastuximab tesirine on D2 of Cycle (C) 1 and then D1 of all other cycles (where each cycle is 21 days). Participants will also receive glofitamab 2.5 mg on C1 D8, 10 mg on C1 D15 and 30 mg for cycles 2-12 D1. In addition participants will receive obinutuzumab pre-treatment 1000 mg on C1 D1.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

ADC Therapeutics S.A.

Lead Sponsor

Trials

32

Recruited

2,700+

Published Research Related to This Trial

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 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]

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]

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 analyzing overall survival (OS) for treatments of relapsed/refractory B-cell lymphomas, tafasitamab combined with lenalidomide showed superior survival outcomes compared to polatuzumab, selinexor, and loncastuximab tesirine, with hazard ratios indicating a significantly lower risk of death.

The analysis utilized reconstructed patient-level data from published survival graphs, providing a comprehensive comparison of these therapies, although the comparisons were indirect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatments for relapsed-refractory diffuse large B-cell lymphoma: comparison of overall survival outcomes observed with four novel agents. Messori, A., Caccese, E.[2022]

In the phase III AUGMENT trial, lenalidomide combined with rituximab significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma compared to placebo, showing particular benefit for elderly patients.

Lenalidomide has an acceptable safety profile, although it can cause more frequent cases of severe neutropenia, which can be managed with dosage adjustments and growth factor support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. Blair, HA.[2021]

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]

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]

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 phase II study involving 145 patients with relapsed or refractory diffuse large B-cell lymphoma, loncastuximab tesirine demonstrated significant improvements in health-related quality of life, with a notable increase in overall health scores over treatment cycles.

The treatment was well-tolerated, with over 60% of patients reporting minimal bother from side effects, indicating a favorable safety profile alongside its antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life, Symptoms, and Tolerability of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Spira, A., Zhou, X., Chen, L., et al.[2022]

Citations

1. Spain pubmed.ncbi.nlm.nih.gov

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

2. United States 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. [2023]

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

Loncastuximab Tesirine: First Approval. [2021]

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. Italy pubmed.ncbi.nlm.nih.gov

Treatments for relapsed-refractory diffuse large B-cell lymphoma: comparison of overall survival outcomes observed with four novel agents. [2022]

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

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. [2021]

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

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

8. 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]

9. 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]

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

Health-Related Quality of Life, Symptoms, and Tolerability of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2022]