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) (topMIND)

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Lymphocytic Leukemia; Non Hodgkin Lymphoma
• Intervention / Treatment: Drug: tafasitamab; Drug: parsaclisib

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, A-4020
    • Ordensklinikum Linz GmbH Elisabethinen
  • Salzburg, Austria, 05020
    • Landeskrankenhaus Salzburg
  • Vienna, Austria, 01140
    • Hanusch-Krankenhaus Der Wiener Gebietskrankenkasse
• Belgium
  • Brussels, Belgium, B-1070
    • Institut Jules Bordet
  • Charleroi, Belgium, 06000
    • Grand hospital de Charleroi
  • Edegem, Belgium, 02650
    • Universitair Ziekenhuis Antwerpen (UZA)
  • Kortrijk, Belgium, 08500
    • AZ Groeninge Campus Kennedylaan
  • Leuven, Belgium, 03000
    • Universitair Ziekenhuis (Uz) Leuven
  • Roeselare, Belgium, 08800
    • AZ Delta
• France
  • Brest, France, 29609
    • University Hospital Brest
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Freiburg im Breisgau, Germany, 79106
    • University Medical Center Freiburg
  • Giessen, Germany, 35392
    • Justus-Liebig University
  • Mainz, Germany, 55131
    • Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
  • Würzburg, Germany, 97080
    • University Hospital Wurzburg
• Italy
  • Bologna, Italy, 40138
    • S Orsolas University Hospital Seragnoli Institute of Hematology
  • Meldola, Italy, 47014
    • Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Naples, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
  • Ravenna, Italy, 48121
    • Ospedale Santa Maria delle Croci
  • Rozzano, Italy, 20089
    • IRCCS Istituto Clinico Humanitas
• Spain
  • Alicante, Spain, 03010
    • Hospital General Unviersitario de Alicante
  • Barcelona, Spain, 08908
    • Ico Institut Catala D Oncologia
  • Barcelona, Spain, 08035
    • Hospital General Universitario Vall D Hebron
  • Barcelona, Spain, 08036
    • Hopital Sant Pau
  • Granada, Spain, 18016
    • Hospital Universitario San Cecilio
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28050
    • Centro Integral Oncológico Clara Campal (CIOCC)
  • Madrid, Spain, 28223
    • Hospital Universitario Quironsalud Madrid
  • Majadahonda, Spain, 28222
    • Hospital Puerta de Hierro
  • Oviedo, Spain, 33011
    • Hospital Universitario Central de Asturias
  • Salamanca, Spain, 37007
    • Hospital Clínico Universitario de Salamanca
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Seville, Spain, 41015
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • California
    • Los Angeles, California, United States, 90089
      • University of Southern California
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood and Marrow Transplantation
    • Indianapolis, Indiana, United States, 46250
      • Community Health Network, Inc.
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Cancer Center For Blood Disorders
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New York
    • New Hyde Park, New York, United States, 11042
      • Clinical Research Alliance
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tafasitamab + parsaclisib; 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; 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.; Other Names: INCMOR00208; Drug: parsaclisib; parsaclisib will be administered at protocol defined dose for cycles 1 through disease progression.; Other Names: INCB050465

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Treatment-emergent Adverse Event (TEAE )	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.	up to 1092 days
Number of Participants With Any ≥Grade 3 TEAE	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.	up to 1092 days
Number of Participants With Dose-limiting Toxicities (DLTs)	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.	up to 28 days
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	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.	up to 1002 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of Tafasitamab When Given in Combination With Parsaclisib	Cmax was defined as the maximum observed plasma or serum concentration of tafasitamab.	Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion
Tmax of Tafasitamab When Given in Combination With Parsaclisib	tmax was defined as the time to the maximum concentration of tafasitamab.	Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion
AUClast of Tafasitamab When Given in Combination With Parsaclisib	AUClast was defined as the area under the plasma concentration-time curve from time zero to the time of the last measurable concentration.	Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion
AUC0-inf of Tafasitamab When Given in Combination With Parsaclisib	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).	Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion
Clast of Tafasitamab When Given in Combination With Parsaclisib	AUC0-inf was defined as the last measurable plasma drug concentration.	Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion
t1/2 of Tafasitamab When Given in Combination With Parsaclisib	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%.	Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion
CL of Tafasitamab When Given in Combination With Parsaclisib	CL was defined as the apparent total body clearance of drug from plasma.	Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion
VZ of Tafasitamab When Given in Combination With Parsaclisib	Vz was defined as the volume of distribution.	Cycle 1 Day 1; before tafasitamab infusion (predose); immediately after tafasitamab infusion; 1 hour and 4 hours post-infusion

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Oliver Manzke, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2021
• Primary Completion (Actual): October 22, 2024
• Study Completion (Actual): October 22, 2024

Study Registration Dates

• First Submitted: March 19, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 22, 2021

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Leukemia; Relapsed or Refractory; MOR00208; INCMOR00208; tafasitamab; parsaclisib
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Lymphoma; Leukemia, Lymphoid; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin; tafasitamab; parsaclisib
• Other Study ID Numbers: INCMOR 0208-101; 2020-005591-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No