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A Phase 1 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 Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03717103
Recruitment Status : Recruiting
First Posted : October 24, 2018
Last Update Posted : December 19, 2018
Sponsor:
Information provided by (Responsible Party):
Innovent Biologics (Suzhou) Co. Ltd.

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.

The study is composed of Ia and Ib phases.


Condition or disease Intervention/treatment Phase
Advanced Malignancies Drug: IBI188 Drug: IBI188, Rituximab Phase 1

Detailed Description:

Phase Ia study is composed of two stages: Phase Ia Part A initial dose escalation and Phase Ia Part B maintenance dose escalation. Both parts will adopt the classical 3+3 dose escalation design.

The starting dose for phase Ia part A 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 14 days.

Phase Ia Part B will have 4 dose cohorts(3mg/kg QW、10mg/kg QW、20mg/kg QW and 30mg/kg QW). DLT observation period is 28 days. The subject number for each cohort in Phase Ia Part B will be increased to 6 if the subject number enrolled in each cohort is less than 6.

Dose level for Phase Ib study will be determined based on the recommended dose from phase Ia.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 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 Malignancies
Actual Study Start Date : December 11, 2018
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : January 31, 2022

Arm Intervention/treatment
Experimental: IBI188 Drug: IBI188

0.1 mg/kg IV QW 0.3 mg/kg IV QW

1 mg/kg IV QW

Other Name: Phase Ia Part A : Initial dose escalation

Drug: IBI188
3 mg/kg IV QW 10 mg/kg IV QW 20 mg/kg IV QW 30 mg/kg IV QW
Other Name: Phase Ia Part B : Maintenance dose escalation

Drug: IBI188, Rituximab
Recommended dose from Ia
Other Name: Phase Ib




Primary Outcome Measures :
  1. Adverse events (AEs), Serious Adverse Events (SAE) [ Time Frame: 2 years ]
    Number of patients with AEs and SAEs


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: up to 2 years after enrollment ]

    To evaluate preliminary anti-tumor activity of IBI188 in subjects with advanced malignancies.

    ORR includes CR and PR assessed by iRECIST v1.1 criteria for solid tumors and Lugano2014 criteria for lymphoma.


  2. Disease Control Rate (DCR) [ Time Frame: up to 2 years after enrollment ]
    To evaluate preliminary anti-tumor activity of IBI188 in subjects with advanced malignancies.

  3. Pharmacokinetics:AUC [ Time Frame: up to 2 years after enrollment ]
    The area under the curve (AUC) of serum concentration of the drug after the administration

  4. Pharmacokinetics: Cmax [ Time Frame: up to 2 years after enrollment ]
    Maximum concentration(Cmax) of the drug after administration

  5. Immunogenicity [ Time Frame: up to 2 years after enrollment ]
    Anti-Drug Antibodies (ADA) will be tested and percentage of ADA positive patients will be calculated to evaluate immunogenicity of IBI188.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Advanced solid tumors and lymphomas defined by:

    • Histologically/cytologically confirmed solid tumors and lymphomas
    • Solid Tumors failed from standard therapy
    • Lymphoma patients who have had at least two standard treatment failures
  2. Subject has at least 1 measurable disease per RECIST v1.1. Lymphomas have at least one measurable lesion and 18FDG-avid lesion according to the Lugano 2014 criteria.
  3. Male or female subject above 18 years
  4. ECOG Performance Status 0 to 1
  5. Must have adequate organ and bone marrow function, including the following:

    • Blood routine: absolute neutrophil count (ANC) ≥ 1.5 x10^9/L; platelet count ≥ 75 x 10^9/L; hemoglobin ≥ 11 g/dL
    • Hepatic: total bilirubin ≤ 1.5 times of the upper limit of normal (ULN), aspartate transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 X ULN (≤5 X ULN if with liver involvement)
    • Renal: serum creatinine ≤ 1.5 X ULN or estimated creatinine clearance ≥50mL/min.
    • Coagulation tests INR < 1.5, partial prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
  6. Subjects with life expectancy of ≥ 12 weeks
  7. Female subjects of child-bearing potential or male subjects with female partners of child-bearing potential must be willing to use viable contraception method that is deemed effective by the investigator throughout the treatment period and for at least 6 months following the last dose of study drug.
  8. Be willing to sign the Informed Consent Form (ICF), and can follow the visit schedule and procedures defined in the protocol.

Exclusion Criteria:

  1. Previous exposure to any anti-CD47 monoclonal antibody or SIRPα antibody.
  2. Subjects participating in any other interventional clinical study
  3. Received blood transfusion, biologic G-CSF, GM-CSF, erythropoietin, thrombopoietin (TPO) or IL-11within 3 weeks prior to the first dose of study drug
  4. Receive the last dose of anti-tumor therapy (chemotherapy, endocrine therapy, targeted therapy, immunotherapy or tumor embolization, etc.) within 3 weeks before the first dose of the study.
  5. Immunosuppressive drugs were used within 7 days before the first dose of the study
  6. Plan to receive live attenuated vaccines within 4 weeks before the first dose treatment or during the study period.
  7. Has undergone major surgery (craniotomy, thoracotomy or laparotomy) or is expected to require major surgery during the first dose of the study.
  8. Any remaining AEs > grade 1 from prior anti-tumor treatment as per CTCAE v5.0, with exception of the residual hair loss nor fatigue
  9. Had received total pelvic radiotherapy before.
  10. Central nervous system metastases:
  11. Subjects with active or suspected autoimmune disease or a history of the disease in the past two years
  12. known history of primary immunodeficiency.
  13. known history of active pulmonary tuberculosis.
  14. known history of allograft transplantation and history of allogeneic hematopoietic stem cell transplantation.
  15. known to be allergic to any IBI188 preparations.
  16. Ascites of clinical significance, including any ascites that may be detected by physical examination, previously treated or still in need of treatment, may be enrolled if only a small amount of ascites is shown on imaging but asymptomatic.

18. Subjects with moderate bilateral pleural effusion, or massive pleural effusion on one side, or respiratory dysfunction requiring drainage.

19. Pregnant or nursing females.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03717103


Locations
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China, Beijing
Beijing Cancer Hospital Recruiting
Beijing, Beijing, China, 100142
Contact: Yuqin Song    +861088196115    SongYQ_VIP@163.com   
Sponsors and Collaborators
Innovent Biologics (Suzhou) Co. Ltd.

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Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
ClinicalTrials.gov Identifier: NCT03717103    
Other Study ID Numbers: CIBI188A101
First Posted: October 24, 2018    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Rituximab
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antirheumatic Agents