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.
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 advanced digestive system carcinoma or neuroendocrine neoplasm 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 oxaliplatin and capecitabine for treatment naïve locally advanced gastric or gastroesophageal junction adenocarcinoma. 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. 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
233
The fifth medical center of the PLA general hospital
Beijing, China
Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
Time frame: Up to 28 days in Cycle 1
Number of All Study Participants Who Demonstrate a Tumor Response
Time frame: Through out the study (up to 2 years)
Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator
ORR was defined as the percentage of participants in the analysis population who had achieved BOR of CR or PR according to RECIST 1.1.
Time frame: Through out the study (up to 2 years)
PFS According to RECIST 1.1 as Assessed by Investigator
Time frame: Through out the study (up to 2 years)
DOR According to RECIST 1.1 as Assessed by Investigator
Time frame: Through out the study (up to 2 years)
TTR According to RECIST 1.1 as Assessed by Investigator
Time frame: Through out the study (up to 2 years)
OS for Participants
Time frame: Through out the study
Area Under the Concentration-time Curve From Zero Time (Predose) to the Time of the Last Measurable Concentration (AUC0-t)
Time frame: Cycle 1: pre-dose, post-dose at 0, 1, and 6 hours, and Days 2, 3, 8, 15, and 22, and 29
Maximum Concentration (Cmax) of Sintilimab in Solid Tumor Participants
Time frame: Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29
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Time to Maximum Concentration (Tmax) of Sintilimab in Solid Tumor Participants
Time frame: Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29
The Half-life (t1/2) of IBI308 in Plasma After Single Dose Administration
Time frame: Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29
Volume of Distribution of IBI308 in Plasma After Single Dose Administration
Time frame: Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29
Clearance of IBI308 in Plasma After Single Dose Administration
Time frame: Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29