PS1073 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
Bibliographic record
Abstract
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 180 mg/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. Summary/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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".