A Study Evaluating Safety, PK, and Efficacy of Tafasitamab and Parsaclisib in Participants With Relapsed/Refractory Non Hodgkin Lymphoma (R/R NHL) or Chronic Lymphocytic Leukemia (CLL)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1b/2a Basket Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Combination Therapy With the Anti CD19 Monoclonal Antibody Tafasitamab and the PI3Kδ Inhibitor Parsaclisib in Adult Participants With Relapsed/Refractory Non Hodgkin Lymphoma or Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia, Non Hodgkin Lymphoma

Intervention / Treatment
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* Drug: tafasitamab
* Drug: parsaclisib


Participation Criteria
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Eligibility Criteria
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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

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: tafasitamab + parsaclisib<br>Participants will be assigned to disease specific cohorts based on the histology of their underlying disease. Cohort 1: R/R DLBCL Cohort 2: R/R MCL Cohort 3: R/R FL Cohort 4: R/R MZL Cohort 5: R/R CLL/SLL | Drug: tafasitamab<br>* 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.<br>* Other names: INCMOR00208;Drug: parsaclisib<br>* parsaclisib will be administered at protocol defined dose for cycles 1 through disease progression.<br>* Other names: INCB050465;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b : Number of Treatment Emergent Adverse Events | Any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. | Up to 25 months | 
| Phase 1b : Incidence of Dose Limiting Toxicities | Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol. All DLTs will be assessed for severity by the investigator using CTCAE v5.0 criteria. | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2a : Overall Response Rate | Defined as the percentage of participants experiencing a best response of Complete Response/Complete Metabolic Response (CR/CMR) or Partial Response/Partial Metabolic Response (PR/PMR) according to the Lugano criteria (Cheson et al 2014) for NHL and the iwCLL criteria (Hallek et al 2018) for CLL. | Up to 25 months | 
| Pharmacokinetics Parameter : Cmax of tafasitamab | Maximum Observed Plasma Concentration of tafasitamab | Up to 24 months | 
| Pharmacokinetics Parameter : Cmin of tafasitamab | Minimum Observed Plasma Concentration of tafasitamab | Up to 24 months | 
| Pharmacokinetics Parameter : Tmax of tafasitamab | Time to reach maximum plasma concentration of tafasitamab | Up to 24 months | 
| Pharmacokinetics Parameter : AUC(t) of tafasitamab | Area under the concentration-time curve from time zero to time of tafasitamab | Up to 24 months | 
| Pharmacokinetics Parameter : Ctrough of tafasitamab | C trough concentration of tafasitamab | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed or Refractory, Leukemia, tafasitamab, parsaclisib, MOR00208, INCMOR00208