PRELIMINARY RESULTS OF ASTX660, A NOVEL NON-PEPTIDOMIMETIC CIAP1/2 AND XIAP ANTAGONIST, IN RELAPSED/REFRACTORY PERIPHERAL T-CELL LYMPHOMA AND CUTANEOUS T CELL LYMPHOMA
Author(s): ,
Amitkumar Mehta
Affiliations:
University of Alabama,Birmingham,United States
,
Antoine Hollebecque
Affiliations:
Institute Gustave Roussy,Villejuif,France
,
Francine Foss
Affiliations:
Yale Cancer Center,New Haven,United States
,
John Lister
Affiliations:
Allegheny Health Network Cancer Institute,Pittsburgh,United States
,
Monica Mita
Affiliations:
Cedars Sinai Medical Center,Los Angeles,United States
,
Nina Wagner-Johnston
Affiliations:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins,Baltimore,United States
,
Martin J.S. Dyer
Affiliations:
Ernest and Helen Scott Haematological Research Institute, University of Leicester,Leicester,United Kingdom
,
Benoit You
Affiliations:
Centre Hospitalier Lyon Sud,Pierre-Bénite,France
,
Anca Prica
Affiliations:
Princess Margaret Cancer Centre,Toronto,Canada
,
Francisco Hernandez-Llizaliturri
Affiliations:
Roswell Park Comprehensive Cancer Center,Buffalo,United States
,
Roberta Ferraldeschi
Affiliations:
Astex Pharmaceuticals, Inc.,Pleasanton,United States
,
Danna Chan
Affiliations:
Astex Pharmaceuticals, Inc.,Pleasanton,United States
,
Jeffrey Zhang
Affiliations:
Astex Pharmaceuticals, Inc.,Pleasanton,United States
Felipe Samaniego
Affiliations:
UT MD Anderson Cancer Centre,Houston,United States
EHA Library. Mehta A. Jun 15, 2019; 266690; PS1073
Amitkumar Mehta
Amitkumar Mehta
Contributions
Abstract

Abstract: PS1073

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
ASTX660 is an oral, novel non-peptidomimetic, small-molecule antagonist of cellular/X-linked inhibitors of apoptosis proteins (cIAP1/2 and XIAP). ASTX660 is currently being evaluated in a first-in-human phase 1‒2 study in patients (pts) with advanced solid tumors and lymphoma (ClinicalTrials.gov NCT02503423). In the phase 1 part of the study, the recommended phase 2 dose (RP2D) was identified with a favorable safety profile and initial evidence of clinical activity in a pt with mycoses fungoides (Mita et al, presented at the AACR-NCI-EORTC Conference 2017, abs #A091).  

Aims
Herein, we report preliminary efficacy and safety results from the ongoing relapsed/refractory (r/r) peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) Phase 2 cohorts.

Methods
Pts receive treatment with ASXT660 at the RP2D 180mg/day on Days 1 to 7, and 15 to 22 in a 28-day cycle. The primary endpoint is response rate as assessed by the investigator according to either the Lugano criteria (PTCL) or Global Assessment (CTCL). Adverse events (AEs) are assessed per CTCAE V4.03. 

Results
As of 15 January 2019, 16 PTCL pts and 13 CTCL pts have received ASTX660. Pt characteristics: median (range) age: PTCL: 59 (39-81) years and CTCL: 57 (23-75) years; median number of prior therapies: PTCL: 3 (1-7) and CTCL: 3 (1-9). In the PTCL cohort the ORR is 28% (4/14); 2 pts have yet to reach their first assessment. Three responding pts remain on study drug for 7-10 months. Responses have been observed in pts with AITL and PTCL-NOS. In the CTCL cohort the global response is 25% (3/12); 1 pt has yet to reach their first assessment. Two responding pts remain on study drug for 4-6 months. Responses have been seen in pts with large cell transformation, sezary syndrome and visceral metastases. Among all pts, the most common related AEs of any grade (≥ 15%) were lipase elevation (38%), amylase elevation (34%), ALT elevation (28%), elevation (24%) and rash (24%). Related AEs ≥ Grade 3 occurring in ≥3 pts were rash (n=5) and lipase elevation (n=4). Accrual continues; updated efficacy and safety results will be presented at the meeting.

Conclusion

In the ongoing Phase 2 cohorts ASTX660 has shown activity against PTCL and CTCL with manageable safety profile. These early data support continued development of ASXT660 for the treatment of r/r PTCL and CTCL. Correlative studies are aimed at identifying predictors of response.

Session topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): Peripheral T-cell lymphoma

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