Phase Ib Study to Assess Safety and Preliminary Efficacy of Tafasitamab or Tafasitamab Plus Lenalidomide in Addition to R-CHOP in Patients With Newly Diagnosed DLBCL

Study Overview
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Brief Summary
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This is an open-label, randomized, multicentre study to evaluate safety and preliminary efficacy of the human anti-CD19 antibody Tafasitamab in addition to R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristin, Prednison) or Tafasitamab and Lenalidomide in addition to R-CHOP in adult patients with newly diagnosed, previously untreated Diffuse Large B-cell Lymphoma (DLBCL).

Official Title
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A Phase Ib, Open-label, Randomized Study to Assess Safety and Preliminary Efficacy of Tafasitamab in Addition to R-CHOP or Tafasitamab Plus Lenalidomide in Addition to R-CHOP in Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) - First-MIND

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: Tafasitamab
* Drug: Tafasitamab plus lenalidomide


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Age >18 years Histologically confirmed diagnosis of DLBCL, not otherwise specified (NOS) Tumor tissue for retrospective central pathology review and correlative studies must be provided. At least one bidimensionally measurable, PET positive disease site (greatest transverse diameter of ≥1.5 cm, greatest perpendicular diameter of ≥1.0 cm) Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 International Prognostic Index (IPI) status of 2 to 5 Appropriate candidate for R-CHOP Left ventricular ejection fraction (LVEF) of ≥50% assessed by echocardiography or cardiac multi-gated acquisition (MUGA) scan Adequate hematologic, liver and renal function Females of childbearing potential (FCBP) must: not be pregnant refrain from breast feeding and donating oocyte agree to ongoing pregnancy testing commit to continued abstinence from heterosexual intercourse, or agree to use and be able to comply with the use of double-barrier contraception Males must: use an effective barrier method of contraception if sexually active with FCBP refrain from donating sperm In the opinion of investigator, the patient must be able and willing to receive adequate prophylaxis and/or therapy for thromboembolic events Major Exclusion Criteria: Any other histological type of lymphoma according to World Health Organization (WHO) 2016 classification of lymphoid neoplasms, known double- or triple-hit lymphoma Transformed non-Hodgkin lymphoma (NHL) and/or evidence of composite lymphoma History of radiation therapy to ≥25% of the bone marrow or history of anthracycline therapy History of prior non-hematologic malignancy except for the following: Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer Adequately treated carcinoma in situ without current evidence of disease History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening arrhythmias Patients with: positive test results for active hepatitis B and C known seropositive for or history of active viral infection with human immunodeficiency virus (HIV) known active bacterial, viral, fungal, mycobacterial, or other infection at screening known central nervous system (CNS) lymphoma involvement history or evidence of clinically significant cardiovascular, CNS and/or other systemic disease that would in the investigator opinion preclude participation in the study

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Tafasitamab in addition to R-CHOP | Drug: Tafasitamab<br>* Six 21-day cycles of tafasitamab (12 mg/kg intravenously, on Day 1, 8 and 15) in addition to R-CHOP<br>|
| Experimental: Arm B<br>Tafasitamab plus lenalidomide in addition to R-CHOP | Drug: Tafasitamab plus lenalidomide<br>* Six 21-day cycles of tafasitamab (12 mg/kg intravenously, on Day 1, 8 and 15) plus lenalidomide (starting dose 25 mg orally, on Day 1-10) in addition to R-CHOP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-emergent adverse events (TEAEs) |  | 6 months approximately | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) at the end of treatment |  | 6 months approximately | 
| Metabolic, PET-negative complete response (CR) rate at the end of treatment |  | 6 months approximately | 
| Incidence and severity of adverse events (AEs) in the follow-up period |  | 18 months approximately | 
| Best Objective Response Rate (ORR) until the end of study |  | 24 months approximately | 
| Metabolic, PET-negative complete response (CR) rate until the end of study |  | 24 months approximately | 
| Progression-free survival (PFS) at 12 and 24 months |  | 24 months approximately | 
| Event-free survival (EFS) at 12 and 24 months |  | 24 months approximately | 
| Time to next anti-lymphoma treatment (TTNT) |  | 24 months approximately | 
| Overall survival at 12 and 24 months |  | 24 months approximately | 
| Anti-tafasitamab antibodies formation |  | 12 months approximately | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DLBCL, CD19, monoclonal antibody, tafasitamab, lenalidomide, MOR208, MOR00208