Study to Evaluate the Efficacy and Tolerability of Debio 1562 in Combination With Rituximab in Participants With Relapsed and/or Refractory DLBCL and Other Forms of NHL

Study Overview
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Brief Summary
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This is an open label, multicenter, adaptive Phase 2 clinical study. The study will consist of a screening period, a treatment period, an end of treatment visit, and a follow-up period.

Official Title
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A Phase 2 Study to Evaluate the Efficacy and Tolerability of Debio 1562 in Combination With Rituximab in Patients With Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma and Other Forms of Non-Hodgkin's Lymphoma

Conditions
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B-cell Non-Hodgkin's Lymphoma, Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Drug: Debio 1562
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Part 1 of the study, participants must have histopathologically confirmed diagnosis of R/R, DLBCL, FL, MZL/MALT, MCL, or other Sponsor approved NHL subtypes according to the World Health Organization (WHO) classification 2008 for which standard measures do not exist or are no longer effective. For Part 2 and Part 3 of the study, participants must have histopathologically and clinically confirmed diagnosis of relapsed DLBCL. Participants will be considered to have a relapsed disease if they showed a duration of response of at least 24 weeks after their first line of therapy. The following participants with relapsed DLBCL will be enrolled: Participants who received at least only one line of previous therapy and achieved either complete response (CR) or partial response (PR) for at least 24 weeks (from the last day of the last cycle) after their first line of therapy, but are not eligible for high dose chemotherapy with autologous stem cell transplantation (HD-ASCT) Participants who received more than one line of previous therapy (including HD-ASCT), and have achieved a duration of response (CR or PR) of at least 8 weeks (from the last day of the last cycle) after their last line of therapy Participants must have evaluable or measurable disease in accordance with the International Working Group Guidelines for Lymphoma. Participants must have received at least one but no more than six prior treatment regimens. Prior treatment with an anti-cluster of differentiation 20 (anti-CD20) agent, either alone or in combination, is allowed. Participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2. Participants who are Hepatitis B surface antigen positive (HBsAg+) (must be polymerase chain reaction (PCR) negative) who are taking antivirals, are allowed to enroll. Exclusion Criteria: Participants with a diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). For Part 2 and Part 3 of the study, participants with primary refractory DLBCL (defined as progression of disease within 24 weeks after first line of treatment). For Part 2 and Part 3 of the study, participants that are eligible to undergo first time HD-ASCT. For Part 2 and Part 3 of the study, participants with R/R FL, MZL/MALT, MCL, or any other NHL subtypes according to the WHO classification. Participants with active hepatitis A, B or C infection. Women who are pregnant or breast feeding. Participants who have received prior therapy with other anti-CD37-targeting therapy. Participants who have known central nervous system, meningeal, or epidural disease including brain metastases. Participants with impaired cardiac function or clinically significant cardiac disease. Participants currently presenting interstitial lung disease, diffuse parenchymal lung disease, or with a past history of severe/Grade 3 parenchymal lung disorders.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Debio 1562<br>Participants with a diagnosis of relapsed and/or refractory (R/R) Diffuse Large B Cell Lymphoma (DLBCL), Follicular Non-Hodgkin's Lymphoma (FL), Marginal Zone Lymphoma (MZL)/Mucosa-associated Lymphoid Tissue (MALT), Mantle Cell Lymphoma (MCL) or other Non-Hodgkin's Lymphoma (NHL) with the Sponsor's approval, will receive Debio 1562 and Rituximab in 3 different parts of study i.e., Safety run in, Part 2 and Expansion (Part 3). Participants in Part 2 will be enrolled in two parallel cohorts (Cohort A and Cohort B). | Drug: Debio 1562<br>* Safety run in: Debio 1562 will be given on the same day as rituximab, once every three weeks (Q3W) intravenously (IV) at the dose of 0.7 mg/kg on Day 1 of a 21-day cycle. Parts 2 and 3: Cohort A- Debio 1562 will be given on the same day as rituximab, once every three weeks (Q3W) intravenously (IV) at the dose of 0.7 mg/kg on Day 1 of a 21-day cycle. Cohort B- Debio 1562 weekly (QW) will be given at a total dose of 0.8 milligram per kilogram (mg/kg) IV over a 21-day cycle. Participants receiving QW regimen will be allowed to switch to Q3W regimen during Coronavirus Disease 2019 (COVID-19) pandemic.<br>Drug: Rituximab<br>* Rituximab will be given on the same day as Debio 1562, Q3W IV at a dose of 375 mg/m^2 on Day 1 of a 21-day cycle in all participants.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | up to 30 months | 
| Objective Response Rate (ORR) | Number of participants with clinical responses as assessed by Lugano Classification of response assessments. | up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma drug concentration (Cmax) of Debio 1562 and Rituximab |  | Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6 | 
| Area under the time-concentration curve from time 0 to t (AUC0-t) of Debio 1562 and Rituximab |  | Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6 | 
| Area under the time-concentration curve from time 0 to infinity (AUC0-inf) of Debio 1562 and Rituximab |  | Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6 | 
| Terminal half-life (t1/2) of Debio 1562 and Rituximab |  | Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6 | 
| Clearance (CL) of Debio 1562 and Rituximab |  | Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6 | 
| Volume of Distribution at Steady State (Vss) of Debio 1562 and Rituximab |  | Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6 | 
| Time to Maximum Plasma Concentration (Tmax) of Debio 1562 and Rituximab |  | Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6 | 
| Progression-free survival (PFS) |  | up to 30 months | 
| Time to response |  | up to 30 months | 
| Duration of response (DOR) |  | up to 30 months | 
| Overall survival (OS) |  | up to 30 months | 
| Number of participants with presence of human anti-drug antibody (ADA) for Debio 1562 |  | Part 1: Pre-dose on Day 1 of Cycles 1-8 (each cycle=21 days); Parts 2 and 3: Pre-dose on Day 1 of Cycles 1-6; and at the end of treatment (Up to Month 36) and 30-day follow-up visit or Day 1 Cycle 7 for participants who received treatment beyond Cycle 6 |