2017 ASCO Annual Meeting!
Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
Type: Poster Session
Time: Monday June 5, 8:00 AM to 11:30 AM
Location: Hall A
A dose-escalation study of imipridone ONC201 administered every one (QW) or three weeks (Q3W) in advanced solid tumors and multiple myeloma.
Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
2017 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #84)
J Clin Oncol 35, 2017 (suppl; abstr 2592)
Author(s): Anthony J. Olszanski, Efrat Dotan, Michael J. Hall, Margaret vonMehren, Eric A. Ross, Amanda M Viereck, Crystal Shereen Denlinger; Fox Chase Cancer Center, Philadelphia, PA
Background: ONC201 is an orally active, first-in-class small molecule activator of the integrated stress response that selectively upregulates ATF4 to trigger tumor cell death. A phase I study of ONC201 exploring different dosing regimens and drug exposure was conducted to determine the maximum tolerated dose (MTD), and recommended phase II dose (RP2D). Methods: A modified accelerated-titration dose escalation design was employed to enroll patients onto 2 sequential dose-escalation arms: ONC201 Q3W and QW. Dose escalation proceeded with the following order: 125, 250, 500, and 625mg (Q3W) and 250, 375, 500 and 625 (QW). Dose exposure ranged from 125 mg/6 wks to 1875 mg/3 wks. Key eligibility: advance/refractory solid tumor or myeloma, ECOG 0/1, and no active CNS disease. Adverse events, SAEs, laboratory values, physical exam findings, EKGs and bio-samples (for PK/PD) are collected. Pre and post ONC201 dose biopsies are being obtained from the 500mg weekly cohort and above. Results: 17 pts (12F:5M) with treatment-refractory tumors have been enrolled to date. Dose/#pts Q3W: 125/6, 250/1, 500/1, and 625/1; QW: 250/4, 375/4. Two patients have been enrolled at 500mg QW after database lock and not included in this assessment. Median (range) age: 57 yrs (27-72). ECOG 0/1: 2/15. MTD has not been reached. No DLTs observed. Tumor types: 8 CRC, 3 pancreatic, 2 sarcoma and 1 each cervical, endometrial, NSCLC (adeno) and small bowel. Of 17 pts, 10 (59%) had ≥1 tx-related adverse events (TRAEs), possibly related. Most common TRAEs (≥15% pts): fatigue (9,53%), anorexia (5,29%), nausea (4,24%), vomiting (4,24%), abdominal pain (3,18%), and arthralgias (2,12%). Grade ≥ 3 TRAEs were observed in 3 pts (18%). Pharmacokinetic and pharmacodynamic analysis is ongoing. Fresh frozen and paraffin-embedded biopsies (baseline and week 2) are being assessed for tumor markers implicated in the mechanism of action. No objective responses by RECIST have been seen. Final cohort is enrolling. Conclusions: ONC201 was well tolerated throughout the Q3W dosing and weekly dosing has been well tolerated to date without an apparent increase in AEs. Final enrollment summary, AEs and PK/PD data will be presented. Clinical trial information: NCT02609230