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J Ji
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Best abstracts selected from submissions 6 (ID 7)
- Event: ACLC 2018
- Type: Oral Session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 11/09/2018, 16:20 - 17:00, Crystal Ballroom 3
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OA12 - A Phase I Study of Novel Bcl-2/Bcl-xL Inhibitor APG-1252 in Patients with Advanced SCLC (ID 220)
16:20 - 17:00 | Author(s): J Ji
- Abstract
Background:
We have developed a unique strategy to tactically reduce on-target platelet toxicity with APG-1252, a novel dual Bcl-2/Bcl-xL inhibitor, while maintaining strong in vivo antitumor activity. APG-1252 potently inhibits tumor growth in human cancer xenograft models including SCLC models while trigged significantly less platelet killing.
Method:
Three clinical studies are ongoing, including two Phase I dose-escalation studies in United States(NCT03080311) and Australia (ACTRN12616001597482), and a Phase I/II study in China (CTR20170976). APG-1252 dose ranging from 10 mg to 400 mg, will be administered via intravenous infusion for 30 minutes, twice weekly, once on Days 1, 4, 8, 11, 15, 18 and 22 in a 28-day-cycle, until disease progression or unacceptable toxicities. Tumor assessment per RECIST is performed every 2 cycles. The primary objective is to assess safety, pharmacokinetics (PK), pharmacodynamics (PD), preliminary efficacy and MTD/RP2D of single-agent APG-1252 in metastatic solid tumors including SCLC.
Results:
As of Aug 31, 2018, 35 patients (including 17 pts with SCLC) have been treated in 6 dose level of APG-1252.The current dose level being explored is 240 mg. Here is a preliminary pool analysis of three studies. APG-1252 was well-tolerated across all dose levels tested. The MTD has not yet been reached. Most adverse events (AE) were mild or moderate in severity, no drug-related AEs leading to drug discontinuation. Only one patient experienced a drug-related serious adverse event (SAE), consisting of a decrease in platelet count was transient and recovered with 72 hours without any treatment or dose interruption. Of 10 SCLC patients who have had at least one post-treatment tumor assessment, one US patient with metastatic SCLC has confirmed partial response (PR) at a dose level of 40mg. After 6 cycles of APG-1252, the target lesion decreased by 44%. The response is durable and this patient has been receiving treatment for 16 cycles. Three patients from China at 80mg dose level had stable disease(SD) after 2 treatment cycles, one of them was confirmed SD. PK analyses indicate that AUC and Cmax increase dose proportionally over 10-160 mg range, AUC and Cmax are comparable between US and Chinese subjects at same dose level.
Conclusion:
APG-1252 was well-tolerated and the MTD has not been reached. Majority of AEs are Grade 1 or 2. No drug-related AE lead to treatment discontinuation. Preliminary anti-cancer effect had been observed in some SCLC patients.
