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295 First-in-human Phase I trial of IBI188, an anti-CD47 targeting monoclonal antibody, in patients with advanced solid tumors and lymphomas
  1. Nehal Lakhani1,
  2. Marlana Orloff2,
  3. Siqing Fu3,
  4. Ying Liu4,
  5. Yan Wang4,
  6. Hui Zhou4,
  7. Kedan Lin4,
  8. Fang Liu4,
  9. Shuling Yan4 and
  10. Amita Patnaik5
  1. 1START MidWest, Grand Rapids, Michigan, USA
  2. 2Thomas Jefferson University (Sarah Cannon), Philadelphia, PA, USA
  3. 3The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  4. 4Innovent Biologics, Inc., Shanghai, China
  5. 5START San Antonio, San Antonio, TX, USA


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

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