TWO-COHORT, PHASE II STUDY IN R/R CLL (COSMOS): FIRST PRELIMINARY SAFETY AND EFFICACY RESULTS OF MOR208 TREATMENT IN COMBINATION WITH IDELALISIB IN PATIENTS WHO DISCONTINUED PRIOR IBRUTINIB THERAPY
Author(s): ,
Wojciech Jurczak
Affiliations:
Department of Hematology,Jagiellonian University,Kraków,Poland
,
Richard Greil
Affiliations:
Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectious Diseases, Rheumatology, Oncologic Center,Paracelsus Medical University Salzburg, Salzburg Cancer Research Institute and Cancer Cluster ,Salzburg,Austria
,
Andrzej Hellmann
Affiliations:
Haematology and Transplantology,Gdanski Uniwersytet Medyczny,Gdansk,Poland
,
Maren Dirnberger-Hertweck
Affiliations:
Morphosys AG,Planegg,Germany
,
Peter Kelemen
Affiliations:
Morphosys AG,Planegg,Germany
,
Johannes Weirather
Affiliations:
Morphosys AG,Planegg,Germany
,
Jan Moritz Middeke
Affiliations:
Medizinische Klinik und Poliklinik I,TU Dresden,Dresden,Germany
,
Marco Montillo
Affiliations:
Niguarda Cancer Center,Niguarda Hospital Milan,Milan,Italy
,
Marina Motta
Affiliations:
S.C. Ematologia,ASST Spedali Civili,Brescia,Italy
,
Peter Neumeister
Affiliations:
Division of Hematology,Medical University of Graz,Graz,Austria
,
Stephan Stilgenbauer
Affiliations:
Department of Internal Medicine III,Ulm University,Ulm,Germany
,
Clemens-Martin Wendtner
Affiliations:
Klinikum Schwabing, Department I of Medicine,Academic Teaching Hospital of University of Munich,Munich,Germany
,
Jennifer Ann Woyach
Affiliations:
Division of Hematology, Department of Internal Medicine,The Ohio State University Comprehensive Cancer Center,Columbus, OH,United States
Johannes Schetelig
Affiliations:
Medizinische Klinik und Poliklinik I,TU Dresden,Dresden,Germany
EHA Library. Jurczak W. Jun 15, 2018; 214823; PF350
Prof. Dr. Wojciech Jurczak
Prof. Dr. Wojciech Jurczak
Contributions
Abstract

Abstract: PF350

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Background

Patients (pts) with relapsed or refractory (R/R) chronic lymphocytic leukaemia (CLL) who failed treatment with Bruton’s Tyrosine Kinase inhibitor (BTKi) ibrutinib have a particularly dismal prognosis. A previous phase I study showed that the Fc-enhanced, humanized, anti-CD19 antibody MOR208 was well tolerated with encouraging single-agent activity in pts with R/R CLL. In preclinical studies, MOR208 showed synergistic potential in combination with idelalisib (IDE, PI3Kδ inhibitor) and venetoclax (VEN, BCL-2 inhibitor).

Aims
This ongoing phase II study assesses the safety and preliminary efficacy of MOR208+IDE (Cohort A) or MOR208+VEN (Cohort B) in pts with R/R CLL previously treated with a BTKi. Here we present the first results of Cohort A.

Methods

Adult pts with R/R CLL without transformation or Richter’s syndrome, who progressed on BTKi therapy or were intolerant to a BTKi during last prior therapy, were eligible in case of having an ECOG status 0–2 and adequate organ function. In Cohort A pts were treated until progression or for up to 24 cycles (C; each C consists of 28 days) with MOR208 administered intravenously at a dose of 12 mg/kg body weight, weekly during C1-3 (with equivalent loading dose on day 4 of C1), every other week in C4-6, monthly in C7-24 and with IDE continuously administered orally at 150 mg BID. Primary endpoint is the incidence and severity of adverse events (AEs), secondary endpoints include overall response rate (ORR) as per IWCLL 2008.

Results

Eleven pts had completed at least 1 cycle of study treatment in Cohort A. Median age: 69 years (51-79); Female 45%; Rai stage ≥3: 36%; Binet stage B/C: 28%/36%; ECOG 0/1: 55%/45%. Nine pts (82%) discontinued prior BTKi treatment due to progressive disease and 2 pts (18%) due to toxicity. The median number of prior treatment lines including ibrutinib was 5 (2-9).  Pts experienced prior FCR chemoimmunotherapy (73%), anti-CD20 mAb (100%) and allogeneic/autologous stem cell transplantation (SCT) (9%/18%). Table 1. summarizes treatment-emergent adverse events (TEAEs). Ten treatment-emergent serious adverse events (SAEs) were reported in 5 pts (45%), none was fatal. All 5 pts recovered, 1 with sequelae after acute pancreatitis. Two pts (18%) permanently discontinued MOR208+IDE due to TEAE (Pt#1: amylase increased Gr4, lipase increased Gr4 and pancreatitis acute Gr4; Pt#2: transaminase increased Gr4). With a median observation time of 4.2 months, investigator assessed ORR was 82 %: 1 CR (9%) confirmed by bone marrow biopsy and 8 PR (73%). Of note, 1 patient with “a very good PR” was taken off the study and received allogeneic SCT. Two pts had progressive disease, 1 of them resulted in fatal cardiorespiratory failure. Two patients who discontinued prior BTKi treatment due to toxicity reached PR, 1 of them discontinued study treatment due to AE. Treatment of 6 pts is ongoing.

Conclusion

The novel combination treatment of MOR208 with idelalisib showed acceptable safety and tolerability as well as promising antitumor activity in heavily pre-treated pts with R/R CLL who failed prior treatment with ibrutinib.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic Lymphocytic Leukemia, ibrutinib, Idelalisib, MOR208

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