A phase I dose-escalation study of BGB-A317, an anti-programmed death-1 (PD-1) mAb in patients with advanced solid tumors.
2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2016.34.15_suppl.3066
ISSN1527-7755
AutoresJayesh Desai, Ben Markman, Shahneen Sandhu, Hui Gan, Michael Friedlander, Ben Tran, Tarek Meniawy, Vishal Boolell, Duncan Colyer, Christie Norris, Malaka Ameratunga, Jason Yang, Kang Li, Lai Wang, Lusong Luo, Zhen Qin, Michael Millward,
Tópico(s)Lung Cancer Research Studies
Resumo3066 Background: BGB-A317 is a humanized IgG4 anti-PD-1 mAb with high specificity and affinity (KD = 0.15 nM) for PD-1. It blocks PD-L1 and PD-L2 binding, and inhibits PD-1-mediated negative signaling in T-cell lines and tumor growth in a number of allogeneic xenograft models. Methods: A phase I, multicenter study was conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and antitumor activity of BGB-A317 in patients (pts) with advanced solid tumors. A 3+3 dose escalation design was undertaken. Pts received escalating doses of BGB-A317 intravenously biweekly (Q2W). Additional pts were treated at 2 and 5 mg/kg either Q2W or Q3W to explore alternate schedules. Results: As of 15 Dec, 2015, 61 patients were treated across 4 dose-escalating cohorts of BGB-A317 Q2W (0.5 mg/kg, n = 3; 2 mg/kg, n = 6; 5 mg/kg, n = 6 and 10 mg/kg, n = 6) and 4 dose-expansion cohorts (2 mg/kg, Q2W, n = 20; 2 mg/kg, Q3W, n = 2; 5 mg/kg Q2W, n = 17 and 5 mg/kg, Q3W, n = 1). One DLT (1/6) of grade 3 colitis was observed in the 5 mg/kg Q2W cohort. Maximum tolerated dose was not reached. The most common treatment-emergent adverse events (AEs) were grade (G) 1-2 fatigue (25%), diarrhea (20%), nausea (16%), rash (13%), pruritus (11%) and abdominal pain (11%). Treatment–related G3 AEs included diabetic ketoacidosis (n = 1, 2 mg/kg Q2W), hypotension (n = 1, 2 mg/kg Q2W), colitis (n = 2, 5 mg/kg Q2W), elevated ALT (n = 1, 2 mg/kg Q2W), hyperglycaemia (n = 1, 2 mg/kg Q2W) and fatigue (n = 1, 5 mg/kg Q2W). PKs of BGB-A317 show dose-proportional exposure increase from 0.5 to 10 mg/kg Q2W after the single dose administration with the elimination half-life of 11 to 17 days. Among 39 evaluable pts to date (10 ovarian, 6 colorectal, 6 RCC, 4 cutaneous SCC, 3 mesothelioma, 2 cervical, and 1 each of 8 others), 3 pts have partial response (2 to be confirmed) (1 gastric, 1 RCC and 1 cervical) and a further 13 pts exhibit stable disease. All 3 responding pts remain on treatment, ranging from 13 to 23 weeks. Conclusions: BGB-A317 demonstrates a favorable safety profile with AEs in keeping with the class effect. PKs are linear and early promising anti-tumor activity has been observed. The expansion cohorts are ongoing and an expanded phase IB study in selected cancer types is planned. Clinical trial information: NCT02407990.
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