Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

First in Human Study of IBI308 in Chinese Subjects With Advanced Solid Tumors

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02937116
Recruitment Status : Active, not recruiting
First Posted : October 18, 2016
Last Update Posted : May 20, 2020
Sponsor:
Information provided by (Responsible Party):
Innovent Biologics (Suzhou) Co. Ltd.

Brief Summary:
The purpose of this study is to determine the safety, tolerability and efficacy of IBI308 monotherapy or in combination with chemotherapy in patients with certain types of advanced solid tumors. Another purpose is to determine the pharmacokinetics, pharmacodynamics and immunogenicity of IBI308

Condition or disease Intervention/treatment Phase
Cancer, Solid Tumor Drug: IBI308 Drug: IBI308\Cisplatinum\Pemetrexed Drug: IBI308\cisplatin\gemcitabine Drug: IBI308\oxaliplatin\capecitabine Drug: IBI308\etoposide\cisplatin Drug: IBI308\irinotecan\5-FU Phase 1

Detailed Description:

This is a study which consists of phase 1a study (dose escalation stage) and phase 1b study (expansion stage). Phase 1a study will adopt the classical 3+3 dose escalation design, exploring safety and tolerance of 4 dose cohorts (1mg/kg, 3mg/kg, 200mg and 10mg/kg) and determining the recommended dose for phase 1b study. Phase 1b is expansion study of 8 cohorts which will evaluate anti-tumor efficacy and safety of eight IBI308 monotherapy or in combination with chemotherapy. Cohort A is IBI308 monotherapy for advanced melanoma. Cohort B is IBI308 monotherapy for malignancies of digestive system after failure or intolerance of first line standard therapy. Cohort C is IBI308 monotherapy for advanced non-small cell lung cancer (NSCLC) after failure or intolerance of first line standard therapy. Cohort D is IBI308 in combination with cisplatin and pemetrexed for treatment-naïve locally advanced, recurrent or metastatic non-squamous NSCLC. Cohort E is IBI308 in combination with gemcitabine and cisplatin for treatment-naïve locally advanced, recurrent or metastatic squamous NSCLC. Cohort F is IBI308 in combination with Cohort G is IBI308 in combination with etoposide and cisplatin for treatment naïve locally advanced, recurrent or metastatic high grade(G3) neuroendocrine tumor. Cohort H is IBI308 in combination with irinotecan and 5-FU for advanced high grade(G3) neuroendocrine tumor after failure of first line standard therapy oxaliplatin and capecitabine for treatment naïve locally advanced, recurrent or metastatic gastric or esophagogastric junction carcinoma.

Phase 1a and 1b consist of screening period (28 days before enrollment), treatment period and follow up period (every 3 months until death or the end of study). In phase 1a, dose limiting toxicity (DLT) will be recorded for up to 28 days after the 1st dose of IBI308. Efficacy will be evaluated by RECIST v1.1. Adverse events will be monitored throughout the study. Further exploration of pharmacokinetic/pharmacodynamics and immunogenicity information will be assessed throughout the trial.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 240 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter Study of IBI308 in Subjects With Selected Advanced Solid Tumors
Actual Study Start Date : October 19, 2016
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2022

Arm Intervention/treatment
Experimental: Phase 1a

Participants will receive IBI308 1mg/kg, 3mg/kg or 10mg/kg intravenous every 2 weeks, or 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity.

Drug: IBI308

Drug: IBI308
Experimental: Phase 1b Cohort A

Participants will receive IBI308 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment.

Drug: IBI308

Drug: IBI308
Experimental: Phase 1b Cohort B

Participants will receive IBI308 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment.

Drug: IBI308

Drug: IBI308
Experimental: Phase 1b Cohort C

Participants will receive IBI308 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment.

Drug: IBI308

Drug: IBI308
Experimental: Phase 1b Cohort D

Participants will receive IBI308 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment.

Drug: IBI308 Drug: Cisplatinum Drug: Pemetrexed

Drug: IBI308\Cisplatinum\Pemetrexed
Experimental: Phase 1b Cohort E
Participants will receive IBI308 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment.
Drug: IBI308\cisplatin\gemcitabine
Experimental: Phase 1b Cohort F
Participants will receive IBI308 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment.
Drug: IBI308\oxaliplatin\capecitabine
Experimental: Phase 1b Cohort G

Participants will receive IBI308 200mg in combination with cisplatin 75mg/m2 intravenously and etoposide 100mg/m2 intravenously day 1 to 3 of every 3 weeks for upto 6 cycles. Those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment.

Drug: IBI308\etoposide\cisplatin

Drug: IBI308\etoposide\cisplatin
Experimental: Phase 1b Cohort H

Participants will receive IBI308 200mg in combination with irinotecan 125mg/m2 intravenously day 1and 8 and 5-FU 1000mg/m2 intravenously day 1 to 3 of every 3 weeks for upto 6 cycles.Those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment.

Drug: IBI308\irinotecan\5-FU

Drug: IBI308\irinotecan\5-FU



Primary Outcome Measures :
  1. Number of participants experiencing dose-limiting toxicities (DLTs) [ Time Frame: Up to 28 days in Cycle 1 ]
  2. Number of all study participants who demonstrate a tumor response [ Time Frame: Trought out the study ]
  3. Number of participants experiencing clinical and laboratory adverse events (AEs) [ Time Frame: Up to 90 days post last dose ]

Secondary Outcome Measures :
  1. The area under the curve (AUC) of plasma concentration of drug against time after administration of IBI308 [ Time Frame: Phase 1a Cycle 1: pre-dose, immediately on finishing infusion, 1, and 6 hours after finishing infusion, and on Days 2, 3, 8, 15, and 22, and 29 ]
  2. Maximum concentration (Cmax) after first dose interval of IBI308 [ Time Frame: Phase 1a Cycle 1: pre-dose, immediately on finishing infusion, 1, and 6 hours after finishing infusion, and on Days 2, 3, 8, 15, and 22, and 29 ]
  3. Time at which maximum concentration (Tmax) occurs for IBI308 [ Time Frame: Phase 1a Cycle 1: pre-dose, immediately on finishing infusion, 1, and 6 hours after finishing infusion, and on Days 2, 3, 8, 15, and 22, and 29 ]
  4. The half-life (t1/2) of IBI308 in plasma after single dose administration [ Time Frame: Phase 1a Cycle 1: pre-dose, immediately on finishing infusion, 1, and 6 hours after finishing infusion, and on Days 2, 3, 8, 15, and 22, and 29 ]


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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
  • Adequate bone marrow, liver, and renal function defined as: 1) Absolute neutrophil count >= 1.5* 10^9 cells/litre (L); 2) Platelets >=100 x 10^9 cells/L; 3) Hemoglobin >= 9 gram/deciliter (g/dL); 4) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 * upper limit of normal (ULN) for participants without hepatic cell cancer and hepatic metastasis, ALT and AST <= 5 * ULN for participants with hepatic cell cancer or hepatic metastasis; 5) Total bilirubin (TBIL) < 1.5 * ULN for participants without hepatic cell cancer, hepatic metastasis and confirmed/suspicious Gilbert syndrome, TBIL < 3 * ULN for participants with hepatic cell cancer, hepatic metastasis or confirmed/suspicious Gilbert syndrome; 6) Creatinine determined by serum creatinine levels <=1.5 * ULN or a calculated creatinine clearance of >= 50 mL/min/1.73 m^2; 7) urine protein -~+, 24 hour urine < 1 gram for participants with urine protein ++ or above; 8) activated partial thromboplastin time and international normalized ratio <= 1.5 * ULN; 9) thyroid stimulating hormone and free thyroxine 4 within normal range
  • Tumor type

    • Phase 1a: advanced solid tumors after failure of standard therapy
    • Phase 1b Cohort A: cytologically or histologically confirmed advanced melanoma
    • Phase 1b Cohort B: cytologically or histologically confirmed advanced malignancies of the digestive system after failure of at least 1 line of standard therapy
    • Phase 1b Cohort C: cytologically or histologically confirmed advanced NSCLC without known epithelial growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement after failure of 1st line standard therapy
    • Phase 1b Cohort D: treatment naive cytologically or histologically confirmed inoperable locally advanced (stage IIIB) or advanced (stage IV) nsNSCLC without known EGFR mutation and ALK rearrangement, participants with disease recurrence or progression within 6 months after completion of prior platinum doublet-based chemotherapy regimen as neoadjuvant or adjuvant therapy are not eligible
    • Phase 1b Cohort E: Cytologically or histologically confirmed, treatment naïve locally advanced, recurrent or metastatic squamous NSCLC without known EGFR mutation and ALK rearrangement. Participants with Stage IIIB NSCLC who progressed within 6 months after completion of platinum-based chemotherapy are not eligible.
    • Phase 1b Cohort F: Histologically confirmed locally advanced, recurrent or metastatic gastric or esophagogastric junction adenocarcinoma without known HER2 amplification.
    • Phase 1b Cohort G: Cytologically or histologically confirmed, treatment naïve locally advanced, recurrent or metastatic high grade(G3) neuroendocrine tumor with Ki-67>20%.
    • Phase 1b Cohort H: Cytologically or histologically confirmed advanced high grade(G3) neuroendocrine tumor with Ki-67>20% after failure of first line standard therapy. Participants progressed within 6 months after completion of adjuvant or neoadjuvant chemotherapy are eligible.
  • At least 1 measurable site of disease per RECIST v1.1

Exclusion Criteria:

  • Prior treatment of any antibody of PD-1 or PD-L1
  • Prior treatment of ipilimumab, unless all the following requirements are met:

    • Full resolution of ipilimumab related adverse effects (including immune related adverse effects) and no treatment for these adverse events (AEs) for at least 4 weeks prior to the time of enrollment
    • Minimum of 12 weeks from the first dose of ipilimumab and >6 weeks from the last dose
    • No history of severe immune related adverse effects from ipilimumab (CTCAE Grade 4; CTCAE Grade 3 requiring treatment >4 weeks)
    • Unequivocal PD following a dose of ipilimumab
  • HIV infection
  • Active HBV or HCV infection
  • Uncontrolled complication including but not limited to :

    • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias or congestive heart failure
    • History of stroke, myocardial infarction or intracranial hemorrhage within 6 months prior to the enrolment
  • History or risk of autoimmune disease
  • Known interstitial lung disease

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): NCT02937116


Locations
Layout table for location information
China
The fifth medical center of the PLA general hospital
Beijing, China
Sponsors and Collaborators
Innovent Biologics (Suzhou) Co. Ltd.
Layout table for additonal information
Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
ClinicalTrials.gov Identifier: NCT02937116    
Other Study ID Numbers: CIBI308A101
First Posted: October 18, 2016    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Gemcitabine
Cisplatin
Capecitabine
Oxaliplatin
Etoposide
Irinotecan
Pemetrexed
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Topoisomerase I Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors