Updated analysis of the inducible T-cell co-stimulatory receptor (ICOS) agonist, GSK3359609 (GSK609), combination with pembrolizumab (PE) in patients (pts) with anti-PD-1/L1 treatment-naïve head and neck squamous cell carcinoma (HNSCC).

6517 Background: INDUCE-1 (NCT02723955) is a first-in-human study investigating GSK609, an IgG4 ICOS agonist non-T-cell depleting antibody, as monotherapy and combination therapy with anti-cancer agents that includes PE. A range of GSK609 dose levels (≥0.1–1 mg/kg) having biological and clinical activity were identified and evaluated in the expansion phase with GSK609 0.3 mg/kg selected as the dose for further investigation. Results from the HNSCC expansion cohorts (ECs) showed GSK609 has single agent activity in pts with relapsed/refractory disease, and early clinical activity in combination with PE in pts with anti-PD-1/L1 treatment-naïve disease (Rischin, et al. Annals of Oncol 2019;30[Supplement_5]:v454–5). Updated results from the GSK609/PE HNSCC EC are presented. Methods: Eligible pts for the HNSCC EC had anti-PD-1/L1 treatment-naïve disease, ≤5 prior lines of therapy, measurable disease, and no active autoimmune disease. Pts received GSK609 0.3 mg/kg + PE 200 mg every 3 weeks (wks) until disease progression or unacceptable toxicity, up to 2 years (yrs)/35 cycles. Disease assessments were performed every 9 wks through wk 54 then every 12 wks thereafter. Pts were followed for survival and subsequent anti-cancer therapy. Results: As of 11 October 2019, 34 pts were enrolled and evaluable for efficacy analyses. The median age of this population was 61.5 yrs (range: 37–77); 85% were male; 53% received ≥1 prior line of therapy in the metastatic setting. ORR was 26% (95% CI: 12.9, 44.4; n = 9 with 4 complete and 5 partial responses); disease control rate was 68% (95% CI: 49.5, 82.6; n = 23). Among pts with PD-L1 IHC status by 22C3 pharmDx assay (n = 24; 71%), the majority of pts with a response or stable disease (SD) had PD-L1 CPS status < 20 (11 of 15 pts including 1 SD pt with CPS < 1). Median PFS was 5.6 months (95% CI: 3.9, 6,2). Median OS was not reached at time of analysis (95% CI: 8.2, NR); 6-month OS rate was 84% (95% CI: 66, 93). Treatment-related adverse events were reported in 66% of pts; the majority of events were Grades 1 or 2 with < 10% of pts experiencing ≥ Grade 3 events. Conclusions: This updated analysis with a more mature dataset shows promising clinical activity that supports further randomized investigation of GSK609 in combination with PE with an OS endpoint in HNSCC. Clinical trial information: NCT02723955 .

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