KD025-208: A PHASE 2 OPEN-LABEL TRIAL OF KD025-208 FOR STEROID-DEPENDENT CHRONIC GRAFT-VERSUS-HOST DISEASE (CGVHD)
Author(s): ,
Madan Jagasia
Affiliations:
Vanderbilt University,Nashville, TN,United States
,
Aleksandr Lazaryan
Affiliations:
University of Minnesota, MN,Minneapolis,United States
,
Amandeep Salhotra
Affiliations:
City of Hope,Duarte, CA,United States
,
Beyhar Zoghi
Affiliations:
Sarah Cannon Research Institute,San Antonio, TX,United States
,
James Essell
Affiliations:
Oncology/Hematology Care,Cincinnati, OH,United States
,
Carlos Bachier
Affiliations:
Sarah Cannon Research Institute,Nashville, TN,United States
,
Beth MacGillivray
Affiliations:
Kadmon Corporation, LLC,New York, NY,United States
,
Olivier Schueller
Affiliations:
Kadmon Corporation, LLC,New York, NY,United States
,
David Eiznhamer
Affiliations:
Kadmon Corporation, LLC,New York, NY,United States
,
John Ryan
Affiliations:
Kadmon Corporation, LLC,New York, NY,United States
Stephanie Lee
Affiliations:
Fred Hutchinson Cancer Research Center ,Seattle, WA,United States
EHA Library. Jagasia M. 06/16/18; 214470; S873
Madan Jagasia
Madan Jagasia
Contributions
Abstract

Abstract: S873

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 16:30 - 16:45

Location: Room A6

Background
KD025 is a ROCK2-selective inhibitor in Phase 2 development for chronic graft-versus-host disease (cGVHD).  By downregulating Th17 and Tfh cells while upregulating regulatory T cells and decreasing myofibroblast formation and proliferation, KD025 targets inflammatory and fibrotic components of cGVHD. 

Aims

The aim is to evaluate the safety and activity of KD025 in subjects with steroid-dependent cGVHD.

Methods
KD025-208 is an open label, Phase 2 study in patients with steroid-dependent or refractory cGVHD.  Three cohorts (200 mg QD, 200 mg BID, and 400 mg QD) of 16 patients each are planned, followed by an expansion cohort.  The primary endpoint is the overall Complete and Partial Response rate, defined per the 2014 NIH Consensus criteria. 

Results
Patients enrolled in Cohorts 1 (n=17) and 2 (n=16) had received a median of 3 and 2 prior lines of cGVHD therapy, respectively.  The median corticosteroid dose (mg/kg/day) at baseline was 0.22 in Cohort 1 and 0.19 in Cohort 2.  The most frequently involved organs in Cohorts 1 and 2, respectively, are eyes (82%, 69%), skin (76%, 75%), mouth (76%, 69%), joints (71%, 69%), and lung (24%, 38%).  Forty-seven percent (47%) of patients in Cohort 1 and 69% in Cohort 2 had involvement of ≥ 4 organs.  Sixteen patients (8 in each cohort) remain on treatment with KD025, with a median treatment duration of 37 and 28 weeks, respectively.  As of a data cutoff date of January 3, 2018, the Overall Response Rate was 65% in Cohort 1 and 69% in Cohort 2.  Responses were rapid, with 68% of responders achieving a response by the first assessment (at 8 weeks).  Seven of 17 patients 41%) in Cohort 1 have sustained a response for ≥ 20 weeks.  In responders with ≥ 4 organs involved, 75% and 33% in Cohorts 1 and 2, respectively, showed response in ≥ 4 organs.  Responses were observed across all affected organ systems, including CRs in upper GI, lower GI, esophagus, mouth, skin, joints, eyes, and liver.  The median corticosteroid dose reduced by 40% in Cohort 1 and 26% in Cohort 2 while on study.  Four patients completely discontinued corticosteroid treatment while receiving KD025.  Sixty-five percent (65%) and 38% of patients in Cohorts 1 and 2, respectively, achieved an improvement (≥ 7 point reduction) in the Lee cGVHD Symptom Scale Score.  KD025 was well tolerated.  Commonly reported AEs were AST/ALT elevations, anemia, nausea, diarrhea and URTI.  Grade 3 or higher AEs were reported in 16 patients and SAEs in 9 patients.  No apparent increase in incidence of infection was observed.  Eleven of 33 patients discontinued treatment due to progression of cGVHD, 1 due to an adverse event, 2 due to recurrence of underlying malignancy, 2 due to voluntary withdrawal, and 1 due to investigator decision. 

Conclusion
Treatment with KD025 has resulted in clinically meaningful and durable overall responses across all affected organ systems.  Corticosteroid doses were reduced in both responders and non-responders.  KD025 treatment was well tolerated with an AE profile consistent with that expected in cGVHD patients receiving corticosteroids.  There was no apparent increased risk of infection observed with KD025.  Enrollment targets in all three cohorts have been reached and treatment is ongoing.  Updated follow-up data will be presented at the meeting.        

Session topic: 23. Stem cell transplantation - Clinical

Keyword(s): Chronic graft-versus-host, Clinical Trial

Abstract: S873

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 16:30 - 16:45

Location: Room A6

Background
KD025 is a ROCK2-selective inhibitor in Phase 2 development for chronic graft-versus-host disease (cGVHD).  By downregulating Th17 and Tfh cells while upregulating regulatory T cells and decreasing myofibroblast formation and proliferation, KD025 targets inflammatory and fibrotic components of cGVHD. 

Aims

The aim is to evaluate the safety and activity of KD025 in subjects with steroid-dependent cGVHD.

Methods
KD025-208 is an open label, Phase 2 study in patients with steroid-dependent or refractory cGVHD.  Three cohorts (200 mg QD, 200 mg BID, and 400 mg QD) of 16 patients each are planned, followed by an expansion cohort.  The primary endpoint is the overall Complete and Partial Response rate, defined per the 2014 NIH Consensus criteria. 

Results
Patients enrolled in Cohorts 1 (n=17) and 2 (n=16) had received a median of 3 and 2 prior lines of cGVHD therapy, respectively.  The median corticosteroid dose (mg/kg/day) at baseline was 0.22 in Cohort 1 and 0.19 in Cohort 2.  The most frequently involved organs in Cohorts 1 and 2, respectively, are eyes (82%, 69%), skin (76%, 75%), mouth (76%, 69%), joints (71%, 69%), and lung (24%, 38%).  Forty-seven percent (47%) of patients in Cohort 1 and 69% in Cohort 2 had involvement of ≥ 4 organs.  Sixteen patients (8 in each cohort) remain on treatment with KD025, with a median treatment duration of 37 and 28 weeks, respectively.  As of a data cutoff date of January 3, 2018, the Overall Response Rate was 65% in Cohort 1 and 69% in Cohort 2.  Responses were rapid, with 68% of responders achieving a response by the first assessment (at 8 weeks).  Seven of 17 patients 41%) in Cohort 1 have sustained a response for ≥ 20 weeks.  In responders with ≥ 4 organs involved, 75% and 33% in Cohorts 1 and 2, respectively, showed response in ≥ 4 organs.  Responses were observed across all affected organ systems, including CRs in upper GI, lower GI, esophagus, mouth, skin, joints, eyes, and liver.  The median corticosteroid dose reduced by 40% in Cohort 1 and 26% in Cohort 2 while on study.  Four patients completely discontinued corticosteroid treatment while receiving KD025.  Sixty-five percent (65%) and 38% of patients in Cohorts 1 and 2, respectively, achieved an improvement (≥ 7 point reduction) in the Lee cGVHD Symptom Scale Score.  KD025 was well tolerated.  Commonly reported AEs were AST/ALT elevations, anemia, nausea, diarrhea and URTI.  Grade 3 or higher AEs were reported in 16 patients and SAEs in 9 patients.  No apparent increase in incidence of infection was observed.  Eleven of 33 patients discontinued treatment due to progression of cGVHD, 1 due to an adverse event, 2 due to recurrence of underlying malignancy, 2 due to voluntary withdrawal, and 1 due to investigator decision. 

Conclusion
Treatment with KD025 has resulted in clinically meaningful and durable overall responses across all affected organ systems.  Corticosteroid doses were reduced in both responders and non-responders.  KD025 treatment was well tolerated with an AE profile consistent with that expected in cGVHD patients receiving corticosteroids.  There was no apparent increased risk of infection observed with KD025.  Enrollment targets in all three cohorts have been reached and treatment is ongoing.  Updated follow-up data will be presented at the meeting.        

Session topic: 23. Stem cell transplantation - Clinical

Keyword(s): Chronic graft-versus-host, Clinical Trial

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