Start Your Search
Y. Le Bruchec
MA 02 - Emerging Targets (ID 656)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Clinical Design, Statistics and Clinical Trials
- Presentations: 1
MA 02.03 - Selective Histone Deacetylase Inhibitor ACY-241 Plus Nivolumab for Refractory Advanced NSCLC: Results From a Phase 1b Study (ID 8189)
11:00 - 12:30 | Author(s): Y. Le Bruchec
ACY-241, an oral inhibitor of histone deacetylase 6, has demonstrated activity in preclinical NSCLC models in combination with immunotherapy. The objectives of this study are to evaluate safety, dose-limiting toxicities (DLTs), the maximum-tolerated dose (MTD), and preliminary antitumor activity of ACY-241 in combination with the immune checkpoint inhibitor nivolumab.
In the 3+3 dose-escalation design, previously treated patients with advanced NSCLC and ECOG PS of 0 or 1 will receive ACY-241 on days 1 to 28 of each 28-day cycle at 3 dose levels (180, 360, and 480 mg) in combination with nivolumab 240 mg on day 15 of cycle 1 and days 1 and 15 of each subsequent cycle. Antitumor activity will be assessed per RECIST v1.1 and immune-related response criteria (irRC).
As of 16 June 2017, 13 patients have been treated in the 3 dose-escalation cohorts. All patients had received first-line treatment with platinum-based chemotherapy. The median age of all patients was 66 years, 62% were male, 54% had an ECOG PS of 0, 54% had stage IV disease, and 85% had adenocarcinoma (15% had squamous histology). No DLTs were observed in the 180- or 360-mg ACY-241 cohorts. The 480-mg cohort is currently under investigation. The most common all-grade adverse events (AEs) in all cohorts were cough (15%), arthralgia (15%), and fatigue (15%, including grade 3 in 1 patient). One patient experienced a grade 3 cerebrovascular accident related to a brain metastasis but unrelated to study drug. No immune-related AEs have been observed. Six patients were evaluable for response: 2 experienced objective responses (1 complete and 1 partial); 2 patients had stable disease; 2 patients had disease progression. Two patients were not evaluable for efficacy, and 5 patients have not yet undergone a response assessment.
No DLTs have been observed with ACY-241 at 180 or 360 mg. Preliminary antitumor activity has been observed with the combination treatment. Updated pharmacokinetic data will be presented at the meeting. NCT02635061
Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.