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4074 Background: In the Phase 3 HIMALAYA study (NCT03298451) of patients (pts) receiving first-line treatment for unresectable hepatocellular carcinoma (uHCC), a single priming dose of tremelimumab (T; anti-CTLA-4) plus durvalumab (D; anti-PD-L1) in the STRIDE regimen significantly improved overall survival (OS) vs sorafenib (S), and D monotherapy was noninferior to S for OS (Abou-Alfa et al. J Clin Oncol 2022;40[suppl 4]. Abs 379). Methods: A pre-planned secondary objective of HIMALAYA was to assess pt-reported outcomes (PROs) in pts receiving STRIDE (T 300 mg plus D 1500 mg [one dose] plus D 1500 mg once every 4 weeks [Q4W]; N=393) or D (1500 mg Q4W; N=389) vs S (400 mg twice daily; N=389). The European Organisation for Research and Treatment of Cancer (EORTC) 30-item Quality of Life (QoL) Questionnaire and the EORTC 18-item HCC QoL questionnaire were used to assess disease-related symptoms, physical functioning (PF), and Global Health Status (GHS)/QoL. Time to deterioration (TTD), defined as time from randomization to first clinically meaningful deterioration (worsening ≥10 points) confirmed at a subsequent visit or death, was assessed in pts with baseline scores ≤90 for symptoms or ≥10 for PF and GHS/QoL. Results: Across treatment arms, compliance rates for PROs were >77% at baseline and >70% overall. Baseline scores were comparable across treatment arms. TTD in fatigue, appetite loss, abdominal pain, PF, and GHS/QoL were significantly longer for both STRIDE and D vs S (Table). TTD in nausea and abdominal swelling were significantly longer for STRIDE vs S. Conclusions: The positive OS outcomes for STRIDE and D in pts receiving first-line treatment for uHCC in HIMALAYA were associated with clinically meaningful, pt-centered benefits, demonstrated by delayed worsening of disease-related symptoms, PF, and GHS/QoL vs S. Median TTD in months (95% CI) in PROs for STRIDE and D vs S. Clinical trial information: NCT03298451. [Table: see text]

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.