topMIND: 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)

Sponsor

Incyte Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04809467

Collaborator

(none)

100

Enrollment

Locations

Arm

25.7

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia Non Hodgkin Lymphoma	Drug: tafasitamab Drug: parsaclisib	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Masking Description:

Open Label

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 16, 2021

Anticipated Primary Completion Date :

Nov 6, 2023

Anticipated Study Completion Date :

Nov 6, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Phase 1b : Number of Treatment Emergent Adverse Events [Up to 25 months]
Any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Phase 1b : Incidence of Dose Limiting Toxicities [28 Days]
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.

Secondary Outcome Measures

Phase 2a : Overall Response Rate [Up to 25 months]
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.
Pharmacokinetics Parameter : Cmax of tafasitamab [Up to 24 months]
Maximum Observed Plasma Concentration of tafasitamab
Pharmacokinetics Parameter : Cmin of tafasitamab [Up to 24 months]
Minimum Observed Plasma Concentration of tafasitamab
Pharmacokinetics Parameter : Tmax of tafasitamab [Up to 24 months]
Time to reach maximum plasma concentration of tafasitamab
Pharmacokinetics Parameter : AUC(t) of tafasitamab [Up to 24 months]
Area under the concentration-time curve from time zero to time of tafasitamab
Pharmacokinetics Parameter : Ctrough of tafasitamab [Up to 24 months]
C trough concentration of tafasitamab

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama At Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35205
2	University of Southern California	Los Angeles	California	United States	90089
3	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana	United States	46237
4	Community Health Network, Inc.	Indianapolis	Indiana	United States	46250
5	Norton Cancer Institute	Louisville	Kentucky	United States	40202
6	Cancer Center For Blood Disorders	Bethesda	Maryland	United States	20817
7	University of Michigan	Ann Arbor	Michigan	United States	48109
8	Clinical Research Alliance	New Hyde Park	New York	United States	11042
9	Ohio State University	Columbus	Ohio	United States	43210
10	Jefferson University Hospitals	Philadelphia	Pennsylvania	United States	19107
11	Ordensklinikum Linz Gmbh Elisabethinen	Linz		Austria	A-4020
12	Landeskrankenhaus Salzburg	Salzburg		Austria	05020
13	Hanusch-Krankenhaus Der Wiener Gebietskrankenkasse	Vienna		Austria	01140
14	Institut Jules Bordet	Brussels		Belgium	B-1070
15	Grand Hospital de Charleroi	Charleroi		Belgium	06000
16	Universitair Ziekenhuis Antwerpen (Uza)	Edegem		Belgium	02650
17	Az Groeninge Campus Kennedylaan	Kortrijk		Belgium	08500
18	Universitair Ziekenhuis (Uz) Leuven	Leuven		Belgium	03000
19	AZ DELTA	Roeselare		Belgium	08800
20	University Hospital Brest	Brest		France	29609
21	Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu	Nantes		France	44093
22	Centre Henri Becquerel	Rouen		France	76038
23	Institut Gustave Roussy	Villejuif		France	94805
24	University Medical Center Freiburg	Freiburg		Germany	79106
25	Justus-Liebig University	Giessen		Germany	35392
26	Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii	Mainz		Germany	55131
27	University Hospital Wurzburg	Wurzburg		Germany	97080
28	S Orsolas University Hospital Seragnoli Institute of Hematology	Bologna		Italy	40138
29	Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori	Meldola		Italy	47014
30	Fondazione Irccs Istituto Nazionale Dei Tumori	Milan		Italy	20133
31	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milan		Italy	20162
32	Istituto Nazionale Tumori Irccs Fondazione Pascale	Naples		Italy	80131
33	Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello	Palermo		Italy	90146
34	Azienda Ospedaliero Universitaria Pisana	Pisa		Italy	56126
35	Ospedale Santa Maria Delle Croci	Ravenna		Italy	48121
36	Irccs Istituto Clinico Humanitas	Rozzano		Italy	20089
37	Hospital General Unviersitario de Alicante	Alicante		Spain	03010
38	Hospital General Universitario Vall D Hebron	Barcelona		Spain	08035
39	Hopital Sant Pau	Barcelona		Spain	08036
40	Ico Institut Catala D Oncologia	Barcelona		Spain	08908
41	Hospital Universitario San Cecilio	Granada		Spain	18016
42	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
43	Centro Integral Oncologico Clara Campal (Ciocc)	Madrid		Spain	28050
44	Hospital Universitario Quironsalud Madrid	Madrid		Spain	28223
45	Hospital Puerta de Hierro	Majadahonda		Spain	28222
46	Hospital Universitario Central de Asturias	Oviedo		Spain	33011
47	Hospital Clinico Universitario de Salamanca	Salamanca		Spain	37007
48	Hospital Universitario Marques de Valdecilla	Santander		Spain	39008
49	Hospital Universitario Virgen Del Rocio	Sevilla		Spain	41015
50	Hospital General Universitario de Valencia	Valencia		Spain	46014