2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
Phase I/Ib study of pembrolizumab and vorinostat in patients with metastatic NSCLC (mNSCLC): Updated results.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #396)
J Clin Oncol 37, 2019 (suppl; abstr 9073)
Author(s): Andreas Nicholas Saltos, Tawee Tanvetyanon, Eric B. Haura, Ben C. Creelan, Scott Joseph Antonia, Michael Rahman Shafique, Hong Zheng, Wenjie Dai, Zhihua Chen, James Joseph Saller, Nishan Tchekmedyian, Kristen Goas, Ram Thapa, Theresa A. Boyle, Dung-Tsa Chen, Amer A Beg, Jhanelle Elaine Gray; Department of Thoracic Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL; Department of Immunology, Moffitt Cancer Center and Research Institute, Tampa, FL; Department of Biostatistics/Bioinformatics, Moffitt Cancer Center and Research Institute, Tampa, FL; Department of Pathology, Moffitt Cancer Center and Research Institute, Tampa, FL; Pacific Shores Medical Group, Huntington Beach, CA
Background: Histone deacetylase inhibitors (HDACi) enhance tumor immunogenicity through several mechanisms and may augment response to immune checkpoint inhibitors (ICI). We report updated results from a phase I/Ib trial testing the combination of oral HDACi vorinostat (V) with PD-1 inhibitor pembrolizumab (P) in mNSCLC. Methods: In phase I, pts with ICI-naïve or ICI-pretreated mNSCLC were treated with P (200mg IV q3 wk) + V (200 or 400 mg PO daily). In phase Ib expansion, pts were required to have progressed on prior ICI treatment. Primary endpoints were safety/tolerability; secondary endpoints included RR, PFS, DOR, and OS. Tissue and blood specimens from pre- and on-treatment were collected for correlative analyses to determine tumor gene expression changes, T cell density and levels of myeloid-derived suppressor cells. Results: Between 3/2016 - 12/2018, Phase I: 13 pts were treated (4 at 200mg, and 9 at 400mg V dose); and Phase Ib: 20 pts were treated. Median age: 68 (range 38-82); Females: 11 (33%); ECOG 1: 31 (94%); and never/former/current smokers: 3/22/8 (9%/67%/24%). PD-L1 expression was < 1% in 8/33 (18%), ≥1-49% in 7/33 (21%), ≥ 50% in 9/33 (27%) and unknown in 11/30 (33%). No DLTs or treatment related deaths were observed. The RP2D was P 200mg and V 400mg. Most common any grade AEs was fatigue (11%) and nausea/vomiting (8%). 2 (6%) patients had treatment discontinued due to toxicity. 30 pts are evaluable for response, 6 ICI-naïve and 24 ICI-pretreated. 4 (13%) had PR (2 confirmed), 16 (53%) had SD, and 10 (33%) had PD for a disease control rate of 67%. In the ICI-pretreated Ib cohort, 3 pts (1 confirmed; 2 unconfirmed) had a PR and 10 had SD (8 confirmed). For ICI-pretreated pts, mPFS was 3.2 and mOS was 7.3 months, and 1-year PFS was 17% (4 pts). For ICI-naïve, mPFS was 7.6 months and mOS was 16 months. CD8 T cell presence in tumor stromal regions was associated with benefit to P + V treatment. Conclusions: P + V were well tolerated. The combination demonstrates preliminary anti-tumor activity despite progression on prior ICI treatment and stromal CD8 T cells may be associated with benefit from P + V treatment. A randomized phase II portion of this study, examining P combined with V vs. placebo in immunotherapy naïve pts, is ongoing. Clinical trial information: NCT02638090