Tuesday, November 13, 2018 10:19:49 AM
www.abstracts2view.com/sabcs18/view.php?nu=SABCS18L_1496
Intratumoral tavokinogene telseplasmid and electroporation in pre-treated inoperable locally advanced or recurrent triple-negative breast cancer
Telli ML, Zablotsky K, Le MH, Canton D, Browning E, Bannavong D, Gargosky S, Wapnir I Stanford University School of Medicine, Stanford, CA; OncoSec Medical, San Diego, CA
Introduction: Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancer diagnoses and is associated with a higher risk of recurrence and more aggressive course in the metastatic setting. Emerging data suggest that some patients with TNBC benefit from immune-based therapies targeting the anti-programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) axis, but success has been limited in poorly immunogenic tumors. Thus, combination therapies that drive an influx of CD8+ tumor infiltrating lymphocytes (TILs) and/or upregulate PD-L1 expression are required to increase response rates to these therapeutics. Intratumoral injection of plasmid IL-12 (tavokinogene telseplasmid; tavo) followed by electroporation (IT-tavo-EP) is a gene therapy approach that drives local expression of the proinflammatory cytokine, interleukin-12 (IL-12). Local expression of IL-12 is hypothesized to result in increased TILs and enhanced expression of proinflammatory cytokines, resulting in conversion of poorly-immunogenic/low TIL TNBC tumors into highly inflamed immunologically active lesions while demonstrating a high safety profile.
Methods: OMS-I140 is a phase I, non-randomized, open-label study of IT-tavo-EP in patients with inoperable locally advanced, metastatic and/or treatment-refractory TNBC (NCT02531425). Eligible patients have pre-treated TNBC and at least 2 anatomically distinct cutaneous or subcutaneous lesions accessible for injection and electroporation, with or without other regional or distant metastases. 10 patients are planned for enrollment. IT-tavo-EP is administered on Days 1, 5 and 8 of a single 28-day cycle. Tavo is injected intratumorally (based on tumor volume) at a concentration of 0.5 mg/mL and immediately followed by co-localized electroporation (6 pulses at 1500 V/cm with 1-second intervals). Tumor biopsies are obtained at baseline and post-treatment on day 28 of both treated and untreated lesions to determine if this therapy can promote a pro-inflammatory molecular and histologic signature. Pain scores and adverse events are recorded.
Results: To date, nine patients have completed study therapy. Reported treatment-related adverse events include pain associated with electroporation (grade 1) in 8 patients and fatigue (grade 1) in 1 patient. Median pain score (range 0-10) immediately after treatment was 2 (range 0-10) and 5 minutes post-treatment was 0 (range 0-6). In some patients, treatment-related increases in CD8+ TIL density have been observed by intratumoral chromogenic staining. Further immune profiling is being conducted to characterize the tumor microenvironment pre- and post-therapy. A subset of patients with treatment refractory TNBC received anti-PD-1 monotherapy as their immediate next therapy with clinical response observed. Updated data will be presented.
Conclusions: Our data suggest that IT-tavo-EP is a safe and tolerable TIL stimulating therapy in TNBC. Further study of IT-tavo-EP in combination with pembrolizumab in pretreated metastatic TNBC is planned.
Session: Poster Session 2: Treatment: Immunotherapy (clinical) (7:30 AM-9:00 AM)
Date/Time: Thursday, December 6, 2018 - 7:30 am
Room: Hall 1
Recent ONCSQ News
- Form SC 13G/A - Statement of acquisition of beneficial ownership by individuals: [Amend] • Edgar (US Regulatory) • 02/13/2024 07:30:19 PM
VHAI - Vocodia Partners with Leading Political Super PACs to Revolutionize Fundraising Efforts • VHAI • Sep 19, 2024 11:48 AM
Dear Cashmere Group Holding Co. AKA Swifty Global Signs Binding Letter of Intent to be Acquired by Signing Day Sports • DRCR • Sep 19, 2024 10:26 AM
HealthLynked Launches Virtual Urgent Care Through Partnership with Lyric Health. • HLYK • Sep 19, 2024 8:00 AM
Element79 Gold Corp. Appoints Kevin Arias as Advisor to the Board of Directors, Strengthening Strategic Leadership • ELMGF • Sep 18, 2024 10:29 AM
Mawson Finland Limited Further Expands the Known Mineralized Zones at Rajapalot: Palokas step-out drills 7 metres @ 9.1 g/t gold & 706 ppm cobalt • MFL • Sep 17, 2024 9:02 AM
PickleJar Announces Integration With OptCulture to Deliver Holistic Fan Experiences at Venue Point of Sale • PKLE • Sep 17, 2024 8:00 AM