9041 Background: A Randomized, Double-blind, Phase III Study was conducted to confirm clinical similarity between BAT1706, a proposed biosimilar to reference bevacizumab, and EU-bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Methods: Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (Arm A) or EU-bevacizumab plus paclitaxel and carboplatin (Arm B) given three weeks for 6 cycles, followed by maintenance therapy with BAT1706 or EU- bevacizumab. The primary endpoint was overall response rate at Week 18 (ORR18). Secondary endpoints included ORR at Week 6 and 12, best ORR, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results: A total of 651 patients were randomized: BAT1706 (n = 325) or EU- bevacizumab (n = 326). In total, 649 randomized patients (BAT1706 (n = 325) or EU- bevacizumab (n = 324)) received at least one cycle of combination treatment. The median duration of therapy was 29.1 weeks (ranging from 3.0 to 62.1 weeks) in the Arm A and 27.0 weeks (ranging from 3.0 to 53.9 weeks) in the Arm B. The extent of exposure to BAT1706 and EU- bevacizumab was similar between these two arms. Overall, the proportion of patients achieving an ORR by Week 18 was comparable across Arm A and B (48.0% and 44.5%). The ORR risk ratio of 1.08 with 90% CI (0.94, 1.24) and the ORR risk difference of 0.03, with 95% CI (-0.04, 0.11) were within pre-specified equivalence margin. In addition, the multivariate-adjusted risk ratio was 1.07, with a 90% CI (0.93, 1.22). The ORR18 risk difference between BAT1706 and EU- bevacizumab was 0.03, with the 2-sided 95% CI (-0.04, 0.11) that fell entirely within pre-specified equivalence margin. In addition, the multivariate-adjusted risk difference was 0.03, with a 95% CI (-0.04, 0.11). The hazard ratio stratified for time to PFS was 0.915 and the PFS rate at 12 months was 20.7% versus 21.8%. At the end of the study, there were no significant differences between both the treatments. The incidence of treatment-emergent adverse events (TEAEs) and study drug-related TEAEs was similar between these two arms. Overall, the safety profiles of BAT1706 were consistent with that of EU- bevacizumab, no new safety signals or noticeable trends were observed. The mean serum concentrations were comparable between BAT1706 and EU- bevacizumab over the entire sampling interval both in pre-dose and post-dose. The incidence of positive anti-drug antibodies results was low (≤5%) and decreased over time in both treatment arms. No patient was detected to have positive neutralizing anti-drug antibody result during the study. Conclusions: BAT1706 demonstrated clinical equivalence to reference EU-bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity. Clinical trial information: NCT03329911.

TPS9137 Background: Immune checkpoint inhibitors have led to durable remissions for some patients with advanced malignancies, including NSCLC; however, only a minority of patients benefit. The field of oncology is addressing this via the development of novel therapies, combinations and identification of biomarkers to select patients most likely to derive clinical benefit. ICOS, a novel therapeutic target, is a costimulatory molecule upregulated on activated T cells. Vopratelimab is an investigational IgG1 ICOS agonist monoclonal antibody that results in activation and proliferation of primed CD4 T effector cells. The preliminary efficacy of vopratelimab +/- nivolumab was assessed in the phase 1/2 ICONIC study in which durable responses were observed in a subset of patients who demonstrated on treatment emergence of peripheral ICOS hi CD4 T effector cells. Patients with peripheral ICOS hi CD4 T cells achieved significantly greater clinical benefit than patients whose CD4 T cells remained ICOS lo. An RNA based tumor inflammation signature (TIS) comprised of 18 genes associated with immune cell infiltration was previously identified as a predictive biomarker of response to anti-PD-1 therapy (Ayers et al, 2017); it was also associated with ICOS hi CD4 T cell emergence in ICONIC (ASCO-SITC 2020). The pre-treatment tumor TIS score, coupled with a specific threshold established by Jounce, referred to as TISvopra, was predictive of ICOS hi CD4 T cell emergence. TISvopra positive patients had improved RECIST response, PFS, and OS compared to those with a TISvopra negative score. Therefore, we hypothesize that patient selection by TISvopra will identify those who will display emergence of ICOS hi CD4 T cell populations and importantly, improved clinical outcomes when treated with vopratelimab in combination with JTX-4014 (a novel PD-1 inhibitor in development by Jounce) vs JTX-4014 alone. Methods: This Phase 2 open-label multicenter study is investigating JTX-4014 alone and in combination with vopratelimab in TISvopra selected patients with metastatic NSCLC after one prior platinum-containing regimen (NCT04549025). Patients must be PD-1/L1 inhibitor naïve and negative for activating EGFR mutations. TISvopra eligibility is determined using RNA isolated from a tumor sample. Eligible patients will be randomized to receive either JTX-4014 as monotherapy or in combination with one of two dose levels of vopratelimab. The primary endpoint is mean percent change from baseline tumor size of all measurable existing and new lesions averaged over 9 and 18 weeks. Secondary endpoints include ORR and PFS according to RECIST v1.1, OS, safety, and association of baseline TIS score with clinical outcomes. The study has a target enrollment goal of approximately 75 patients; the first patient was dosed October 2020. Clinical trial information: NCT04549025.