Study to Evaluate Safety and Preliminary Efficacy of Tafasitamab With Idelalisib or Venetoclax in R/R CLL/SLL Patients Pretreated With BTKi

Study Overview
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Brief Summary
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This is a two-cohort, multicenter, open-label study of tafasitamab (MOR208) combined with idelalisib or venetoclax in adult patients with R/R CLL or R/R SLL pretreated with a BTK inhibitor (e.g., ibrutinib) as single agent or as part of combination therapy. Patients completing the study treatment are invited to participate in an optional biomarker sub-study.

Detailed Description
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The purpose of this study is to evaluate the clinical safety and preliminary efficacy of tafasitamab (MOR208) combined with idelalisib or venetoclax. The study will include safety run-in phase for each cohort with an evaluation of the safety data by an Independent Data Monitoring Committee. An optional sub-study has been introduced to collect biological samples for investigations on biomarkers (e.g., CD19 expression) after tafasitamab treatment.

Official Title
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A Phase II, Two-Cohort, Open-Label, Multicenter Study to Evaluate the Safety and Preliminary Efficacy of MOR00208 Combined With Idelalisib or Venetoclax in Patients With Relapsed or Refractory CLL/SLL Previously Treated With Bruton's Tyrosine Kinase (BTK) Inhibitor

Conditions
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Leukemia, Lymphocytic, Chronic, B-Cell, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Biological: Tafasitamab
* Drug: Idelalisib
* Drug: Venetoclax


Participation Criteria
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Eligibility Criteria
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Major inclusion criteria Diagnosis/Trial Population Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL): history of diagnosis of CLL or SLL that meets IWCLL diagnostic criteria histologically confirmed diagnosis of SLL by lymph node biopsy indication for treatment as defined by the IWCLL guidelines Patients must have both of the following: relapsed or refractory disease while receiving a BTKi therapy or intolerance of such therapy single-agent or combination therapy with a BTKi for at least one month must be the patient's most recent prior anticancer therapy ECOG performance status of 0 to 2 Patients with a past medical history of autologous or allogeneic stem cell transplantation must exhibit full hematological recovery Laboratory Values • Patients must meet adequate bone marrow function and adequate hepatic and renal function Other Inclusion Criteria • Females of childbearing potential must use a highly effective method of contraception Major exclusion criteria Diagnosis • Patients who have: non-Hodgkin's lymphomas other than CLL/SLL transformed CLL/SLL or Richter's syndrome active and uncontrolled autoimmune cytopenia Previous and Current Treatment Patients who have received treatment with a BTK inhibitor within 5 days prior to Day 1 dosing Patients who have, within 14 days prior to D1 dosing: not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day with the exception of patients with signs of rapidly progressing disease received live vaccines with the exception of vaccination against influenza with inactivated virus or for pneumococcal diseases

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>tafasitamab (MOR208) in combination with idelalisib | Biological: Tafasitamab<br>* tafasitamab (MOR208) dose: 12 mg/kg intravenous infusion<br>* Other names: MOR00208;Drug: Idelalisib<br>* idelalisib dose: 150 mg twice daily orally<br>* Other names: Zydelig; GS-1101 or CAL-101;|
| Experimental: Cohort B<br>tafasitamab (MOR208) in combination with venetoclax | Biological: Tafasitamab<br>* tafasitamab (MOR208) dose: 12 mg/kg intravenous infusion<br>* Other names: MOR00208;Drug: Venetoclax<br>* venetoclax dose: 400 mg once daily orally<br>* Other names: Venclexta, Venclyxto; ABT-199;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Adverse Events (AEs) | For details please see Section of Adverse Events Overview | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Objective Response Rate (ORR) | ORR = complete response [CR] + partial response [PR]; Local Evaluation | 2 years | 
| Number of Participants With Treatment-emergent or Treatment-boosted Anti-MOR00208 Antibody Formation | Number of participants with treatment-emergent or treatment-boosted anti-MOR00208 (anti-tafasitamab) antibody formation | 2 years | 
| Maximum Plasma Concentration (Cmax) of MOR00208 | Mean Cmax of tafasitamab (MOR00208) at Cycle 3 Day 15 (after the weekly dosing of tafasitamab in Cycles 1 to 3 including a loading dose at C1D4) | At Cycle 3 Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD19, MOR208, MOR00208, CLL, SLL, COSMOS, tafasitamab