Chronic Lymphocytic Leukemia, Non Hodgkin Lymphoma
Conditions
Keywords
Relapsed or Refractory, Leukemia, tafasitamab, parsaclisib, MOR00208, INCMOR00208
Brief summary
The purpose of this single-arm, open-label, Phase 1b/2a, multicenter basket study is to evaluate whether tafasitamab and parsaclisib can be safely combined at the recommended Phase 2 dose (RP2D) and dosing regimen that was established for each of the 2 compounds as a treatment option for adult participants with R/R B-cell malignancies.
Interventions
DRUGtafasitamab
tafasitamab will be administered at a protocol defined dose once a week for cycles 1-3 and every other week from cycle 4 until progression.
DRUGparsaclisib
parsaclisib will be administered at protocol defined dose for cycles 1 through disease progression.
Sponsors
Incyte Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed R/R B-cell malignancy: DLBCL (THRLBCL, EBV-positive DLBCL of the elderly, Grade 3b FL, HGBL with MYC and BCL2 and/or BCL6 rearrangements, transformed lymphoma); MCL ((with cyclin D1 overexpression or t(11;14); FL (Grade 1, 2, 3a); MZL (extranodal, nodal, splenic) ; CLL, or SLL * Willingness to undergo biopsy * At least 2 prior systemic treatment regimens, including prior treatment with an anti-CD20 antibody (all cohorts) or prior treatment with a BTK inhibitor (CLL/SLL) * Relapsed, progressive, or refractory NHL or CLL * For NHL/SLL: Radiographically measurable nodal or extranodal disease (all cohorts except CLL) * ECOG-PS 0 - 2 * LVEF ≥ 50% * Adequate renal, hepatic, bone marrow function
Exclusion criteria
* Any other histological type of lymphoma * Primary or secondary CNS lymphoma * Anticancer and/or investigational therapy within the past 30 days or 5 half-lives * Allogeneic stem cell transplantation within the past 6 months, or ASCT within 3 months before C1D1 * Previous treatment with CD19-targeted therapy or PI3K inhibitors * Clinically significant cardiac disease * Other malignancy within the past 3 years * Active graft-versus-host disease * Stroke or intracranial hemorrhage within the past 6 months * Chronic or current active infectious disease * Positive virus serology for HCV, HBV, HIV * Currently pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE ) | up to 1092 days | An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE is any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 90 days after the last dose of study drug. |
| Number of Participants With Any ≥Grade 3 TEAE | up to 1092 days | An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered drug related. A TEAE is any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 90 days after the last dose of study drug. The severity of AEs was assessed using CTCAE v5.0 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal. |
| Number of Participants With Dose-limiting Toxicities (DLTs) | up to 28 days | A DLT was defined as the occurrence of any protocol-defined toxicity up to and including Day 28 (Cycle 1/Day 28), except those with a clear alternative explanation. |
| Objective Response Rate Based on Investigator Assessment: Percentage of Participants With CR/CMR or PR/PMR According to Lugano Criteria for NHL and International Working Group for Chronic Lymphocytic Leukemia (iwCLL) Criteria for CLL | up to 1002 days | Lugano complete response/complete metabolic response (CR/CMR): target nodes/masses of lymph nodes/extralymphatic sites (LNs/ELSs) regressed to ≤1.5 cm; no non-measured lesions; organ enlargement regressed to normal; no new lesions (NNLs); normal bone marrow. Lugano partial response/partial metabolic response (PR/PMR): LNs/ELSs, ≥50% decrease in the product of perpendicular diameters sum for multiple lesions; no/regressed non-measured lesions, no increase; organ enlargement; NNLs. iwCLL CR: no LNs ≥1.5 cm; spleen size \<13 cm/liver size normal; no constitutional symptoms; normal circulating lymphocyte count (CLC); ≥100 × 10\^9 platelets/L; hemoglobin ≥11 g/dL; normocellular, no CLL cells, no B-lymphoid nodules in marrow. iwCLL PR decrease of ≥50% in lymph nodes, liver and/or spleen, and CLC from baseline; constitutional symptoms; ≥100 × 10\^9 platelets/L or increase of ≥50% over baseline in platelet count and hemoglobin; presence of CLL cells, or of B-lymphoid nodules, or not done. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Tafasitamab When Given in Combination With Parsaclisib | Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion | Cmax was defined as the maximum observed plasma or serum concentration of tafasitamab. |
| Tmax of Tafasitamab When Given in Combination With Parsaclisib | Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion | tmax was defined as the time to the maximum concentration of tafasitamab. |
| AUClast of Tafasitamab When Given in Combination With Parsaclisib | Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion | AUClast was defined as the area under the plasma concentration-time curve from time zero to the time of the last measurable concentration. |
| AUC0-inf of Tafasitamab When Given in Combination With Parsaclisib | Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion | AUC0-inf was defined as the area under the plasma concentration-time curve from time zero to infinity (time that the drug is no longer present in the body). |
| Clast of Tafasitamab When Given in Combination With Parsaclisib | Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion | AUC0-inf was defined as the last measurable plasma drug concentration. |
| t1/2 of Tafasitamab When Given in Combination With Parsaclisib | Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion | t1/2 was defined as the drug's elimination half-life, which is the time it takes for the concentration of a drug in the body to decrease by 50%. |
| CL of Tafasitamab When Given in Combination With Parsaclisib | Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion | CL was defined as the apparent total body clearance of drug from plasma. |
| VZ of Tafasitamab When Given in Combination With Parsaclisib | Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion | Vz was defined as the volume of distribution. |
Countries
Austria, Belgium, France, Germany, Italy, Spain, United States
Contacts
STUDY_DIRECTOROliver Manzke, MD
Incyte Corporation
Participant flow
Pre-assignment details
Participants were enrolled across 16 sites in Austria, Belgium, Spain, France, and Italy. Enrollment was not fully completed due to a strategic decision by the sponsor to discontinue further enrollment in the study based on the changing treatment landscape with respect to the use of PI3Kδ inhibitors (including but not limited to parsaclisib) for treatment of NHL. Therefore the expansion phase was not opened.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 68.9 years STANDARD_DEVIATION 15.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 15 | 7 / 11 | 4 / 21 | 0 / 3 | 1 / 4 |
| other Total, other adverse events | 15 / 15 | 11 / 11 | 21 / 21 | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 6 / 15 | 7 / 11 | 12 / 21 | 2 / 3 | 3 / 4 |
Outcome results
None listed