Long Term Follow-up of a Phase 2 Study Examining Intratumoral G100 Alone and in Combination with Pembrolizumab in Patients with Follicular Lymphoma

Background: Despite numerous treatment (Tx) options, follicular lymphoma (FL) remains incurable, and established common treatments such as chemoimmunotherapy combinations and kinase inhibitors can have significant morbidity, especially in older patients or in those with comorbidities. G100 is a TLR4 (toll-like receptor 4) agonist that activates both the innate and adaptive arms of the immune system. When given intratumorally (IT), G100 triggers an anti-tumor immune response that leads to systemic tumor shrinkage (Flowers ASCO 2017). Initial data from a randomized study of the combination of G100 and pembrolizumab (P) demonstrated that the addition of P resulted in more PRs, abscopal tumor shrinkage, and a trend to a better PFS than G100 alone. In addition, an association between baseline tumor TLR4 expression by immunohistochemistry (IHC) and clinical response was observed (Flowers ASH 2017). We now present updated response data and long-term follow-up of this randomized study.Methods: Previously treated or Tx naïve FL pts with ≥2 tumor sites were eligible. Pts received 6-9 doses of IT G100 (G) weekly to a site treated with low dose radiation (RT, 2 Gy x2 doses). A 2nd course of G could be given without additional RT to an additional site. Pts were randomized to IT G (10 µg/dose) or IT G + P 200mg IV on Day 14 then q3wks for up to 2 years. Responses were evaluated by IrRC criteria based on bidimensional measurements (Wolchok ClCanRes 2009). Untreated sites were followed for abscopal response.Results: As of 3July2018, 26 FL pts were treated (13, G vs. 13, G + P). 7 and 5 pts were Relapsed/Refractory (R/R) in G and G+P, respectively. Median number of prior therapies were 3 for G and 4 for G+P and included 5pts previously Tx with auto-SCT. Median duration of observation was 14.3 and 16.6 mos for the G and G+P, respectively. G was well tolerated; related AEs were all grade (Gr) 1/ 2 with no G-related DLTs or SAEs. For G+P, 1 pt experienced Gr 2 hypothyroidism and 1pt, Gr 3 colitis/lab abnormalities/adrenal insufficiency (SAE). No deaths were reported.Overall best responses (PRs) were: 23% in pts on G and 54% in pts on G+P. In the R/R population, PRs occurred in 29% of pts on G and in 80% of pts on G+P. Median time to response was 2.3 mos (range 1.7-18.1) for G and 3.7 mos (range 2.2-17.1) for G+P, and included delayed responses at ≥18mos. Among pts with baseline TLR4high (≥50%) tumor expression, ORR was 17% for G (n=6) vs 75% for G+P (n=8). Within the GELF high tumor burden pts, PRs occurred in 0% of pts in G and in 33% of pts in G+P. Likewise, in pts failing R-Chemo