RT Journal Article
SR Electronic
T1 383 Durable responses with intratumoral electroporation of plasmid interleukin 12 plus pembrolizumab in patients with advanced melanoma progressing on an anti-PD-1 antibody: updated data from keynote 695
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP A417
OP A417
DO 10.1136/jitc-2021-SITC2021.383
VO 9
IS Suppl 2
A1 Pablo Fernandez-Penas
A1 Matteo Carlino
A1 Katy Tsai
A1 Victoria Atkinson
A1 Monaster Shaheen
A1 Sajeve Thomas
A1 Catalin Mihalcioiu
A1 Tom Van Hagen
A1 Rachel Roberts-Thomson
A1 Andrew Haydon
A1 Andrew Mant
A1 Marcus Butler
A1 Gregory Daniels
A1 Elizabeth Bunchbinder
A1 John Hyngstrom
A1 Mecker Moller
A1 Igor Puzanov
A1 C Lance Cowey
A1 Eric Whitman
A1 Carmen Ballesteros-Merino
A1 Shawn Jensen
A1 Bernard Fox
A1 Emmett Schmidt
A1 Scott Diede
A1 Rebecca Setta
A1 Jendy Sell
A1 David Canton
A1 Sandra Aung
A1 Christopher Twitty
A1 Sunny Xie
A1 Ying Lu
A1 Bridget O’Keefe
A1 Alain Algazi
A1 Adil Daud
YR 2021
UL http://jitc.bmj.com/content/9/Suppl_2/A417.abstract
AB Background Electroporated plasmid interleukin-12 (pIL-12-EP; tavokinogene telseplasmid; TAVO) induces sustained intratumoral expression of IL-12, a cytokine that is integral for response to anti-PD-1 antibodies. Here, we present updated safety and response duration data from KEYNOTE 695, a Phase 2, multicenter, open-label trial of pIL-12-EP in combination with pembrolizumab in patients with stage III/IV melanoma immediately following confirmed progression on an anti-PD-1 antibody.Methods Patients with confirmed disease progression after ≥12 weeks‘ treatment with an anti-PD-1 antibody alone or in combination were eligible. Patients received intratumoral pIL-12-EP on days 1, 5 and 8 every 6 weeks and pembrolizumab 200 mg every 3 weeks. Responses were assessed by the investigator at 12-week intervals using RECIST v1.1; overall survival (OS) and duration of response (DoR) assessments were conducted using the Kaplan-Meier method.Results Of the first 56 patients treated, 50% had visceral disease (M1b-d), 80% had received 1–2 and 20% ≥3 prior lines of therapy, 27% had prior ipilimumab and 21% prior BRAF/MEK inhibitors. 61% of patients were primary refractory to anti-PD-1. 54 patients were efficacy evaluable, defined as patients who had at least one post-treatment scan. The investigator-assessed objective response rate (ORR) per RECIST was 27.8% (4 CR, 11 PR); ORR per iRECIST was 29.6%. In patients with M1b-d staging, ORR was 33.3% (n=9/27), and in those receiving prior ipilimumab, ORR was 33.3% (n=5/15). Seven patients had 100% reduction in target lesions, and regression was observed in non-injected lesions. The median DoR had not been reached. With a median follow up of 19.3 months, the median OS (95% CI) was 24.5 (14.4, NR) months (figure 1). The study is now fully enrolled. In 105 patients with safety data, there were no Grade 4/5 treatment-related adverse events (TRAEs) reported. Grade 3 TRAEs occurred in 5.7% and comprised cellulitis in two patients and arthralgia, pneumonitis, enteritis, keratoacanthoma, lichen planus and musculoskeletal chest pain in one patient each. The Grade 1/2 TRAEs in ≥10% patients were fatigue (27.6%), procedural pain (20.0%), diarrhea (17.1%), nausea (10.5%) and pruritus (10.5%). ORR by blinded independent central review has commenced and a global phase 3 trial is planned.Abstract 383 Figure 1 Overall survival in patients treated with pIL-12-EP in combination with pembrolizumab. Dark grey bars: time on study treatment, light grey bars: end of treatment to death or censoringConclusions Patients with anti-PD-1 therapy refractory advanced melanoma can achieve deep, durable responses in both injected and non-injected lesions with pIL-12-EP plus pembrolizumab. Intratumoral pIL-12-EP in combination with pembrolizumab was generally well tolerated, with minimal Grade 3 and no Grade 4/5 TRAEs.Trial Registration NCT03132675Ethics Approval The study was approved by a central IRB and/or local institutional IRB/Ethics Committee as required for each participating institution.Consent Written informed consent was obtained from the patients participating in the trial; the current abstract does not include information requiring additional consent