Evaluate Safety and Efficacy of Loncastuximab Tesirine and Ibrutinib in DLBCL and MCL
Research type
Research Study
Full title
A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of Loncastuximab Tesirine and Ibrutinib in Patients with Advanced Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma (LOTIS-3)
IRAS ID
1003472
Contact name
John Radford
Contact email
Eudract number
2018-002625-38
Clinicaltrials.gov Identifier
Research summary
Research Summary
Patients with Diffuse large B-cell lymphoma (DLBCL) and Mantle cell lymphoma (MCL)
who have relapsed have poorer outcomes. Most patients respond well to first-line therapy
but relapse soon after highlighting the need for more effective treatments for patients
who do not respond well to standard treatment.
Loncastuximab tesirine (ADCT-402) is an antibody drug conjugate (ADC), which is a
type of medicine that combines an antibody (a protein that binds to specific substances in
the body) against a protein found on the surface of lymphoma cells (CD19) with a
chemotherapy drug that has the ability to kill cells. Expression is maintained blood
cancers such as DLBCL and MCL. Ibrutinib is an inhibitor of Bruton’s tyrosine kinase
(BTK), a protein ), important in B-cell signalling, which is usually implicated in the
pathogenesis of a variety of B-cell malignancies including MCL.
Loncastuximab tesirine and ibrutinib have shown activity as single agents but only a
minority of patients will have a complete response to either treatment; and some patients
will relapse at some point after treatment. Using a combination of both agents has the
potential to increase the anti-tumour response and reduce the occurrence of relapse,
compared to either agent alone.
This is a global, open-label, multi-centre phase 1/2 study designed to assess the safety
and anti-tumour activity of Loncastuximab Tesirine and Ibrutinib in adult patients with
DLBCL and MCL. Up to 161 participants may be involved with 55 participants in Phase
1 and 106 participants in Phase 2. Participants will continue to receive study treatment
for up to 1 years or until disease progression, unacceptable toxicity, consent withdrawal,
investigator decision, study termination by the sponsor, pregnancy or death, whichever
occurs first. This study will take place in approximately 16 sites worldwide.Summary of results
Patients with Diffuse large B-cell lymphoma (DLBCL) and Mantle cell lymphoma (MCL) who have relapsed have poorer outcomes. Most patients respond well to first-line therapy but relapse soon after, highlighting the need for more effective treatments for patients who do not respond well to standard treatment. Loncastuximab tesirine (ADCT-402) is an antibody drug conjugate (ADC), which is a type of medicine that combines an antibody (a protein that binds to specific substances in the body) against a protein found on the surface of lymphoma cells (CD19) with a chemotherapy drug that has the ability to kill cells. CD19 is present on the surface of certain blood cancer cells, such as DLBCL and MCL Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK), a protein), important in B-cell signalling, and can be involved in the development of blood cancers, including DLBCL and MCL. Loncastuximab tesirine and ibrutinib have shown activity when used alone but only a minority of patients will have a complete response to either treatment and some patients will relapse after treatment. Using a combination of both treatments has the potential to increase the activity against cancer cells and reduce the occurrence of relapse, compared to either treatment alone. This was a global, open-label, multi-centre phase 1/2 study designed to assess the safety and anti-tumour activity of Loncastuximab Tesirine and Ibrutinib in adult patients with DLBCL and MCL. A total of 136 participants across 36 centres in 6 countries were enrolled in the study. In Part 1 of the study, 47 participants received loncastuximab tesirine at doses of either 60, 75 or 90 micrograms per kilogram of bodyweight every 21 days, in combination with daily doses of ibrutinib. Participants received up to 4 doses of loncastuximab tesirine and received ibrutinib for up to 1 year. Because of the side effects at the highest dose tested, and because no important side effects were seen at the lower doses, the 60 microgram per kilogram dose was selected for further testing in Part 2 on the study. The proportion of patients who responded to treatment in this part of the study was 57.4%. In Part 2 of the study, 89 participants received loncastuximab tesirine at a dose of 60 micrograms per kilogram of body weight every 21 days, in combination with daily doses of ibrutinib. Participants received up to 6 doses of loncastuximab tesirine and received ibrutinib for up to 1 year. The proportion of patients who responded to treatment in this part of the study was 53.4%. The most common side effects reported in the study were temporary decreases in blood cells. There were no new or important side effects when loncastuximab tesirine and ibrutinib were used in combination, compared to the treatments given alone. Although the combination of loncastuximab tesirine plus ibrutinib has resulted in encouraging activity in DLBCL and MCL, the sponsor decided to focus on other combinations that will better serve patients and the medical community. Therefore, this study was stopped early, but not due to safety reasons.
REC name
South Central - Hampshire A Research Ethics Committee
REC reference
20/SC/0398
Date of REC Opinion
18 Dec 2020
REC opinion
Further Information Favourable Opinion