Background: ASTX660 is an oral, novel nonpeptidomimetic, 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 data from the 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 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 data will be presented at the meeting.
Conclusion: In 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.
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