Phase I/II study of CTLA-4 inhibitor AGEN1884 + PD-1 Inhibitor AGEN2034 in patients with advanced/refractory solid tumors, with expansion into 2L cervical cancer and solid tumors

Abstract

Background: Cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and programmed death 1 (PD-1) pathways have important, distinct roles in T-cell modulation; blockade of both has been synergistic in vitro and in the clinic. This study will assess safety and tolerability of AGEN1884 (anti-CTLA-4 human immunoglobulin [IgG]-1 monoclonal antibody [mAb]) in combination with AGEN2034 (anti-PD-1 human IgG4 mAb) in patients (pts) with advanced/refractory solid tumors, with expansion into select solid tumors. Methods: A dose-escalation phase and expansion focusing on adult female pts with recurrent/metastatic cervical cancer that has relapsed after platinum-containing doublet treatment. Phase 1 (Ph1) pts (n=20) will be enrolled to 2 dose regimens of AGEN1884 + AGEN2034 (starting: 1 mg/kg AGEN1884 Q6w+ 1 mg/kg AGEN2034 Q2w; escalating: 1 mg/kg AGEN1884 Q6w+ 3 mg/kg AGEN2034 Q2w). Escalation phase primary endpoints: safety, determination of recommended Ph2 dose (RP2D); Ph2 (n=40) also includes best overall response assessment by Independent Endpoint Review Committee per RECIST 1.1. Secondary endpoints: AGEN1884 and AGEN2034 pharmacokinetic (PK)/pharmacodynamic (PD) profiles, objective response rate, duration of response, progression-free and overall survival. Results: 0 pts were enrolled 01Dec2017-10Apr2018 in 3 Australia centers: 7 pts at starting dose, 3 pts at escalating dose. No dose-limiting toxicity has been observed; most common toxicities observed were expected for therapeutic class. 8 pts experienced toxicity, mostly grade 1 or 2.Most common toxicities: diarrhea/nausea/vomiting, n=6; rash/pruritus, n=2; transaminases elevated, n=1; fever/flu-like, n=3; fatigue, n=2. There was 1 serious adverse event and grade 3 toxicity unrelated to study drug. No discontinuation due to study drug, no deaths observed. Median dose administered was 1 for AGEN1884, 3 for AGEN2034. Dose level 2 was determined for RP2D. Updated safety, efficacy, and PK/PD of AGEN1884 + AGEN2034 will be presented. Conclusions: AGEN1884 (1 mg/kg Q6w) + AGEN2034 (3 mg/kg Q2w) is well tolerated and being evaluated in Ph2 combination in 2L cervical cancer and other solid tumors.