A Study of IBI310 in Treatment of Patients With Advanced Solid Tumors.

Overview

This is an open-label, dose escalation, Phase I study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and efficacy of single agent of IBI310 and in combination of sintilimab in patients with advanced solid tumors(Ia) and advanced melanoma(Ib).

Full Title of Study: “A Phase I, Open-Label Study to Investigate the Tolerability and Safety of IBI310 Alone or in Combination With Sintilimab in Treatment of Patients With Advanced Solid Tumors.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 15, 2021

Detailed Description

Phase Ia study will adopt the classical 3+3 dose escalation design. The starting dose is 0.3 mg/kg, followed by 3 dose cohorts (1mg/kg, 2mg/kg and 3mg/kg). Duration of dose limiting toxicity observation is 21 days. IBI310 treatment q3w, up to 3 cycles, will be provided to patients who complete DLT observation period.

Efficacy will primarily be evaluated by RECIST v1.1. Patients' safety will be monitored throughout the study. Pharmacokinetic/pharmacodynamics and immunogenicity will be assessed throughout the study.

Phase Ib study on the tolerability and safety of IBI310 combined with Sintilimab in patients with advanced melanoma. Phase Ib of the study will begin after DLT observation is completed in certain dose cohorts.

Interventions

  • Drug: IBI310
    • IBI310 is anti CTLA-4 antibody
  • Drug: Sintilimab
    • PD-1 monoclonal antibody

Arms, Groups and Cohorts

  • Experimental: Ia Cohort A
    • Low-dose group:Participants will receive IBI310 0.3mg/kg intravenous every 3 weeks,after 4 cycle, if the patient benefits it will be continued until disease progression or unacceptable toxicity.
  • Experimental: Ia Cohort B
    • Middle-dose group:Participants will receive IBI310 1.0mg/kg intravenous every 3 weeks,after 4 cycle, if the patient benefits it will be continued until disease progression or unacceptable toxicity
  • Experimental: Ia Cohort C
    • Middle-dose group:Participants will receive IBI310 2.0mg/kg intravenous every 3 weeks,after 4 cycle, if the patient benefits it will be continued until disease progression or unacceptable toxicity
  • Experimental: Ia Cohort D
    • High-dose group:Participants will receive IBI310 3.0mg/kg intravenous every 3 weeks,after 4 cycle, if the patient benefits it will be continued until disease progression or unacceptable toxicity
  • Experimental: Ib Cohort A
    • 3 subjects, low-dose group:Participants will receive IBI310 1.0mg/kg in Combination with Sintilimab 200mg intravenous every 3 weeks. After 4 cycles, Sintilimab alone 200mg intravenous every 3 weeks, until disease progression, lost follow-up visit, death , unacceptable toxicity, withdrawn of ICF, another other reason for end of treatment. Maximum treatment duration is 2 years.
  • Experimental: Ib Cohort A2
    • low-dose group:Participants will receive IBI310 1.0mg/kg in Combination with Sintilimab 200mg intravenous every 3 weeks. After 4 cycles, Sintilimab alone 200mg intravenous every 3 weeks, until disease progression, lost follow-up visit, death , unacceptable toxicity, withdrawn of ICF, another other reason for end of treatment. Maximum treatment duration is 2 years.
  • Experimental: Ib Cohort B
    • 3 subjects, low-dose group:Participants will receive IBI310 2.0mg/kg in Combination with Sintilimab 200mg intravenous every 3 weeks. After 4 cycles, Sintilimab alone 200mg intravenous every 3 weeks, until disease progression, lost follow-up visit, death , unacceptable toxicity, withdrawn of ICF, another other reason for end of treatment. Maximum treatment duration is 2 years.
  • Experimental: Ib Cohort B2
    • low-dose group:Participants will receive IBI310 2.0mg/kg in Combination with Sintilimab 200mg intravenous every 3 weeks. After 4 cycles, Sintilimab alone 200mg intravenous every 3 weeks, until disease progression, lost follow-up visit, death , unacceptable toxicity, withdrawn of ICF, another other reason for end of treatment. Maximum treatment duration is 2 years.

Clinical Trial Outcome Measures

Primary Measures

  • AEs
    • Time Frame: up to 24 months after randomization
    • Number of patients with treatment-related adverse events (AEs)

Secondary Measures

  • Pharmacokinetics:Cmax
    • Time Frame: up to 24 months after randomization
    • Maximum concentration(Cmax) of the drug after administration
  • pharmacodynamics:lipid parameters
    • Time Frame: up to 24 months after randomization
    • Change from baseline in lipid parameters
  • ADA
    • Time Frame: up to 24 months after randomization
    • Number of participants with anti-drug antibodies or neutralizing antibodies
  • Pharmacokinetics:AUC
    • Time Frame: up to 24 months after randomization
    • The area under the curve (AUC) of serum concentration of the drug after the administration

Participating in This Clinical Trial

Key Inclusion Criteria:

1. Patients with locally advanced, recurrent or metastatic solid tumors who failed standard treatment(applicable to the Ia period).

2. Patients with advanced, recurrent or metastatic melanoma confirmed by cytology or histology (applicable to the Ib period).

3. Signed written informed consent form and willing and able to comply with scheduled visits and other requirements of the study.

4. ≥18,and ≤70 years.

5. Life expectancy of at least 12 weeks.

6. At least 1 measurable lesion per RECIST v1.1(long axis>15mm or short axis>10mm)

7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1.

8. Patients of reproductive potential must be willing to use adequate contraception during the course of the study and through 6 months after the last dose of study medication.

9. Adequate organ and bone marrow function.

Key Exclusion Criteria:

1. Prior exposure to any anti-CTLA-4, anti-PD-1 or anti-PD-L1/L2 antibody.

2. Received any investigational agent within 4 weeks of the first dose of study medication.

3. Received last dose of anti-tumor therapy (chemotherapy, endocrine therapy, targeted therapy, tumor immunotherapy or arterial embolization) within 4 weeks of the first dose of study medication.

4. Received treatment with corticosteroids (>10mg daily prednisone equivalent) or other immunosuppressive medications within 4 weeks before the first dose of study medication. Nasal spray, inhalation, or other ways of topical corticosteroids or physiological doses of systemic corticosteroids are not included.

5. Received a live vaccine within 4 weeks of the first dose of study medication or plan to receive live vaccine during study period.

6. Active, known or suspected autoimmune disease or has a history of the disease within the last 2 years (Patients with vitiligo, psoriasis, alopecia or Grave's disease, hypothyroidism requiring hormone replacement, or type I diabetes mellitus only requiring insulin replacement, but not required systemic treatment in the last 2 years, are permitted to enroll)

7. Known primary immunodeficiency

8. Active tuberculosis

9. Known history of allogeneic organ or allogeneic hemopoietic stem cell transplantation

10. Known allergy or hypersensitivity to any other monoclonal antibodies or IBI310 and/or any components used in their preparation.

11. Known acute or chronic active hepatitis B (HBV DNA positive and HBV DNA copies ≥1×103/ml or ≥200IU/ml) infection or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive) infection. Patients with HCV antibody positive but HCV RNA negative are permitted to enroll.

12. Patients with a history of interstitial lung disease

13. Uncontrolled third space effusion, eg. ascites or pleural effusion cannot be drained or controlled.

14. Women who are pregnant or nursing.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Innovent Biologics (Suzhou) Co. Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Jingxia Suo, 0512-69566088, jingxia.suo@innoventbio.com

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