295 First-in-human Phase I trial of IBI188, an anti-CD47 targeting monoclonal antibody, in patients with advanced solid tumors and lymphomas. (9th November 2020)

• Record Type: Journal Article
• Authors: Lakhani, Nehal; Orloff, Marlana; Fu, Siqing; Liu, Ying; Wang, Yan; Zhou, Hui; Lin, Kedan; Liu, Fang; Yan, Shuling; Patnaik, Amita
• Is Part Of: Journal for immunotherapy of cancer. Volume 8(2020)Supplement 3
• Page Start: A322
• Page End: A322
• Publication Date: 2020-11-09
• Subjects: Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2020-SITC2020.0295
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: IBI188 is a humanized IgG4 monoclonal antibody targeting CD47, an antiphagocytic ('don't eat me') signal present on cancer cells. Blockage of this myeloid checkpoint, IBI188 enhances tumor cell phagocytosis and cross priming of T-cells. We conducted a first-in-human phase 1a trial to evaluate the tolerability, safety and PK/PD characteristics of IBI188. (NCT03763149 ). Methods: Patients with advanced/refractory solid tumors or lymphoma were enrolled in this two-part dose-escalation study: Part A for testing optimal priming doses at 0.1, 0.3, and 1 mg/kg and Part B for optimal maintenance doses at 3, 10, 20, 30 mg/kg weekly. An accelerated titration followed by traditional 3+3 design was used in this study with a 28-day dose-limiting toxicity (DLT) observation period. Primary endpoint was safety profile; secondary endpoints included PK parameters and PD markers, i.e. CD47 receptor occupancy. Results: As of June 18, 2020, 20 patients have been enrolled, 6 in Part A and 14 in Part B. There was no DLT reported at any dose level. The median treatment duration was 1.8 months (0.2–5.5) months. The most common treatment-related adverse events (TRAEs) were nausea (n=7), back pain (n=7), fatigue (n=6), vomiting (n=4) and blood bilirubin increased (n=4). Three patients had ≥ Grade 3 TRAEs (Grade 3 blood bilirubin increase, Grade 4 platelet count decrease and Grade 3 anemia, each in 1 patient). Three of 20 patients (15%) had anemia, an expected TRAE associated with the mechanism of IBI188. Majority of the patients (65%) had infusion related reactions (IRR). All IRRs were Grade 1–2 and able to be managed with standard IRR treatment. The clearance of IBI188 decreased with the increasing dose from 3 to 20 mg/kg and IBI188 can overcome the sink at 10 mg/kg or higher dose level. The PK analysis at 30 mg/kg is ongoing. The 10 mg/kg maintenance dose resulted in T cells receptor occupancy above 80%. After multiple administrations (≥ 3 times, including the priming dose), the RBC and T cells receptor occupancy tends to be stable and maintained around 90%. The receptor occupancy analysis at 20 mg/kg and 30 mg/kg is ongoing. Conclusions: IBI188 was well tolerated at 1 mg/kg priming dose following by the maintenance dose up to 30 mg/kg. Trial Registration: NCT03763149