Chronic Lymphocytic Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell, Small Lymphocytic Lymphoma
Conditions
Keywords
CD19, MOR208, MOR00208, CLL, SLL, COSMOS, tafasitamab
Brief summary
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
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.
Interventions
BIOLOGICALTafasitamab
tafasitamab (MOR208) dose: 12 mg/kg intravenous infusion
DRUGIdelalisib
idelalisib dose: 150 mg twice daily orally
DRUGVenetoclax
venetoclax dose: 400 mg once daily orally
Sponsors
MorphoSys AG
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Adverse Events (AEs) | 2 years | For details please see Section of Adverse Events Overview |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Objective Response Rate (ORR) | 2 years | ORR = complete response \[CR\] + partial response \[PR\]; Local Evaluation |
| Number of Participants With Treatment-emergent or Treatment-boosted Anti-MOR00208 Antibody Formation | 2 years | Number of participants with treatment-emergent or treatment-boosted anti-MOR00208 (anti-tafasitamab) antibody formation |
| Maximum Plasma Concentration (Cmax) of MOR00208 | At Cycle 3 Day 15 | 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With MRD-negativity | 2 years | Proportion of patients who reached MRD-negativity in peripheral blood |
Countries
Austria, Germany, Italy, Poland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A (Tafasitamab+Idelalisib) Tafasitamab in combination with idelalisib | 11 |
| Cohort B (Tafasitamab+Venetoclax) Tafasitamab in combination with venetoclax | 13 |
| Total | 24 |
Baseline characteristics
| Characteristic | Cohort A (Tafasitamab+Idelalisib) | Cohort B (Tafasitamab+Venetoclax) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 5 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 8 Participants | 11 Participants |
| Age, Continuous | 69 years | 64 years | 65 years |
| Number of previous systemic treatment lines | 5 Lines | 3 Lines | 4 Lines |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 13 Participants | 24 Participants |
| Region of Enrollment Austria | 2 participants | 4 participants | 6 participants |
| Region of Enrollment Germany | 3 participants | 1 participants | 4 participants |
| Region of Enrollment Italy | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Poland | 5 participants | 0 participants | 5 participants |
| Region of Enrollment United Kingdom | 0 participants | 2 participants | 2 participants |
| Region of Enrollment United States | 0 participants | 6 participants | 6 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 11 | 0 / 13 |
| other Total, other adverse events | 11 / 11 | 12 / 13 |
| serious Total, serious adverse events | 8 / 11 | 9 / 13 |
Outcome results
Primary
Incidence and Severity of Adverse Events (AEs)
For details please see Section of Adverse Events Overview
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A (Tafasitamab+Idelalisib) | Incidence and Severity of Adverse Events (AEs) | 11 Participants |
| Cohort B (Tafasitamab+Venetoclax) | Incidence and Severity of Adverse Events (AEs) | 13 Participants |
Secondary
Best Objective Response Rate (ORR)
ORR = complete response \[CR\] + partial response \[PR\]; Local Evaluation
Time frame: 2 years
Population: Intention-to-treat patient population consists of all enrolled patients. As per study protocol all patients were required to have computed tomography (CT) scans of the neck, chest, abdomen and pelvis to determine tumor response. These were performed at screening, at Day 1 of Cycles 4, 7, 13, and 19, etc. and at end-of-treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A (Tafasitamab+Idelalisib) | Best Objective Response Rate (ORR) | Intention-to-treat patient population | 90.9 Percentage of participants |
| Cohort A (Tafasitamab+Idelalisib) | Best Objective Response Rate (ORR) | Pts with tumor response assessment by CT | 90.9 Percentage of participants |
| Cohort B (Tafasitamab+Venetoclax) | Best Objective Response Rate (ORR) | Intention-to-treat patient population | 76.9 Percentage of participants |
| Cohort B (Tafasitamab+Venetoclax) | Best Objective Response Rate (ORR) | Pts with tumor response assessment by CT | 100 Percentage of participants |
Secondary
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)
Time frame: At Cycle 3 Day 15
Population: All patients with available pharmacokinetic data for Cmax at Cycle 3 Day 15.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A (Tafasitamab+Idelalisib) | Maximum Plasma Concentration (Cmax) of MOR00208 | 278379.9 ng/mL | Standard Deviation 118746.34 |
| Cohort B (Tafasitamab+Venetoclax) | Maximum Plasma Concentration (Cmax) of MOR00208 | 306998.9 ng/mL | Standard Deviation 41254.2 |
Secondary
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
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A (Tafasitamab+Idelalisib) | Number of Participants With Treatment-emergent or Treatment-boosted Anti-MOR00208 Antibody Formation | 0 Participants |
| Cohort B (Tafasitamab+Venetoclax) | Number of Participants With Treatment-emergent or Treatment-boosted Anti-MOR00208 Antibody Formation | 0 Participants |
Other Pre-specified
Proportion of Patients With MRD-negativity
Proportion of patients who reached MRD-negativity in peripheral blood
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A (Tafasitamab+Idelalisib) | Proportion of Patients With MRD-negativity | 1 Participants |
| Cohort B (Tafasitamab+Venetoclax) | Proportion of Patients With MRD-negativity | 6 Participants |