Background: AGEN1884 is a novel fully human IgG1 monoclonal antibody targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Objective: Assess the safety, maximum tolerated dose, and pharmacokinetic (PK) and pharmacodynamic characteristics of AGEN1884 in patients with advanced and refractory malignancies. Methods: Patients (≥18 years old) with relapsed/refractory lymphoma or solid cancers without curative treatment options received AGEN1884 at 0.1, 0.3, 1, 3 or 6 mg/kg in a “3+3” trial design. An additional 10 patients were enrolled in both 1 and 3 mg/kg dose expansion cohorts. AGEN1884 was administered intravenously (IV) every 3 weeks for 4 doses and then every 3, 6, or 12 weeks at the Investigator’s discretion. Results: As of 03Jan2018 data cutoff, 33 patients were enrolled in the following cohorts: 0.1 mg/kg (n = 5, 2 not evaluable [NE] for dose-limiting toxicity [DLT]), 0.3 mg/kg (n = 3), 1 mg/kg (n = 10), 3 mg/kg (n = 12, 2 NE for DLT) and 6 mg/kg (n = 3). Median age was 61 years (range 26–88), baseline ECOG scores were 0 (N = 4), 1 (N = 25), unknown (4), with a median of 10 (range 3–26) prior therapies. As of Jan 31, 2018, no DLT’s have been reported. Immune-related adverse events were reported in 10 (30.3%) of patients as follows: 0.1 mg/kg (1 [20.0%]), 0.3 mg/kg (1 [33.3%]), 1 mg/kg (1 [10%]), and 3 mg/kg (6 [50%]) and included hypophysitis, colitis, diarrhea, rash and pruritus. Most were mild-moderate consistent with published reports of other CTLA-4 inhibitors. 6 patients (18.2%) came off study due to disease progression or AE’s but none related to treatment. Of 11 subjects evaluable for response, 1 with angiosarcoma treated at 0.1 mg/kg attained a CR at 7 months after achieving a PR. Three subjects with SD: 1 at 0.3 mg/kg with adenoid cystic carcinoma at Week 21 who had SD for 53 weeks; 2 subjects at 3 mg/kg: 1 with breast cancer with SD at Week 6 and 1 with invasive metaplastic breast cancer at Week 12 on study. Conclusions: AGEN1884 was well tolerated at 0.1, 0.3, 1 and 3 mg/kg dose levels. Enrollment continues at 6 mg/kg. Updated safety and PK data will be presented. A starting dose level of 1 mg/kg has been selected for combination with PD-1 blockade. Clinical trial information: NCT02694822