A Phase 1a Study Evaluating the Safety, Tolerability, and Initial Efficacy of Recombinant Human Anti-cluster Differentiation Antigen 47 (CD47) Monoclonal Antibody Injection (IBI188) in Patients With Advanced Malignant Tumors and Lymphomas

Innovent Biologics (Suzhou) Co. Ltd.4 sites in 1 country20 target enrollmentFebruary 19, 2019

ConditionsAdvanced Malignancies

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Advanced Malignancies
Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
Enrollment: 20
Locations: 4
Primary Endpoint: Number of patients with AEs and SAEs
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, dose escalation, Phase I study to evaluate the safety, tolerability, pharmacokinetics and efficacy in patients with advanced malignancies.

Detailed Description

The study is composed of two stages: Part 1 Accelerated Titration Phase and Part 2 Dose Escalation Phase with initial fixed priming dose. The starting dose for part 1 is 0.1 mg/kg QW, followed by 2 dose cohorts (0.3 mg/kg QW and 1 mg/kg QW). Duration of dose limiting toxicity (DLT) observation is 28 days. Part 2 will have 4 dose cohorts(3mg/kg QW、10mg/kg QW、20mg/kg QW and 30mg/kg QW). Conventional 3+3 Dose Escalation will be adopted. DLT observation period is 28 days.

Registry

clinicaltrials.gov

Start Date

February 19, 2019

End Date

March 29, 2021

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Innovent Biologics (Suzhou) Co. Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Able to understand and willing to sign the ICF.
•Male or female subject above18 years.
•Histologically/cytologically confirmed, locally advanced unresectable or metastatic solid tumors and lymphomas that are refractory to standard therapy, or for which no standard therapy exists.
•For dose expansion at the RP2D: subject has measurable disease per RECIST v1.
•that was not in a prior radiation area within past 6 months, unless tumor growth was documented following radiation. Lymphomas have at least one measurable lesion and FDG-avid lesion according to the Lugano 2014 criteria.
•Separate informed consent for subjects who provide archived tissue biopsies for biomarker testing (Optional).
•ECOG Performance Status 0 to 1
•Subjects with life expectancy of ≥ 3 month
•No herbal/alternative medications within 14 days prior to the first dose of IBI
•Must have adequate organ function, prior to start of IBI188, including the following:

Exclusion Criteria

•Pregnant or nursing females.
•Any remaining AEs \> grade 1 from prior anti-tumor treatment as per CTCAE v5.0, with exception of the residual hair loss;
•Received a biologic G-CSF, GM-CSF or erythropoietin within 14 days prior to the first dose of study drug;
•Subjects participating in any other interventional clinical study
•Previous exposure to any anti-CD47 monoclonal antibody or SIRPα antibody.
•Subjects who had transfusion within 3 weeks
•Patients who are on anticoagulants and /or require concomitant aspirin or other nonsteroidal anti-inflammatory medications.
•Subjects who have a history of documented autoimmune disease, even if not clinically severe or never treated with systemic steroids or immunosuppressive agents, are not candidates for this clinical trial, except for autoimmune hypothyroidism and well-controlled Type 1 diabetes mellitus.
•Subjects with or w/o autoimmune condition requiring systemic treatment with either corticosteroids (\>10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days before the planned first dose of study drug. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. Ophthalmologic, nasal and intra-articular injections or steroids are acceptable.
•Subject with primacy central nervous system (CNS) malignancy or symptomatic CNS metastases are not allowed. Subjects with asymptomatic CNS metastases are eligible if clinically controlled, which is defined as ≥8 weeks of stable neurologic function following CNS-directed therapy, and no evidence of CNS disease progression as determined by radiographic imaging ≥ 4 weeks prior to screening. No interim progression between the completion of CNS-directed therapy and the screening tumor assessment, and ≥ 2 weeks from discontinuation of anti-seizure and steroid therapies from screening.

Outcomes

Primary Outcomes

Number of patients with AEs and SAEs

Time Frame: 2 years

To evaluate the safety and tolerability of IBI188 \[Adverse events (AEs), Serious Adverse Events (SAE) \]

Secondary Outcomes

Preliminary anti-tumor activity of IBI188 (Objective Response Rate)(up to 2 years after enrollment)
Pharmacokinetics: AUC(up to 2 years after enrollment)
Pharmacokinetics: Cmax(up to 2 years after enrollment)
Immunogenicity: Percentage of ADA positive patients(up to 2 years after enrollment)