Cancer, Solid Tumor
Conditions
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.
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 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.
Interventions
DRUGIBI308
DRUGIBI308\Cisplatinum\Pemetrexed
DRUGIBI308\cisplatin\gemcitabine
DRUGIBI308\oxaliplatin\capecitabine
DRUGIBI308\etoposide\cisplatin
DRUGIBI308\irinotecan\5-FU
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Dose-limiting Toxicities (DLTs) | Up to 28 days in Cycle 1 | — |
| Number of All Study Participants Who Demonstrate a Tumor Response | 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 | Through out the study (up to 2 years) | 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. |
Secondary
| Measure | Time frame |
|---|---|
| OS for Participants | Through out the study |
| Area Under the Concentration-time Curve From Zero Time (Predose) to the Time of the Last Measurable Concentration (AUC0-t) | 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 | Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29 |
| PFS According to RECIST 1.1 as Assessed by Investigator | Through out the study (up to 2 years) |
| The Half-life (t1/2) of IBI308 in Plasma After Single Dose Administration | 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 | 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 | Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29 |
| Time to Maximum Concentration (Tmax) of Sintilimab in Solid Tumor Participants | Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29 |
| DOR According to RECIST 1.1 as Assessed by Investigator | Through out the study (up to 2 years) |
| TTR According to RECIST 1.1 as Assessed by Investigator | Through out the study (up to 2 years) |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3 |
| Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3 |
| Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3 |
| Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | 3 |
| MEL: Sintilimab 200mg Q3W (Cohort A) Subjects received sintilimab 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. | 22 |
| Malignant Tumor of the Digestive System or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) Subjects received sintilimab 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. | 87 |
| NSCLC: Sintilimab 200mg Q3W (Cohort C) Subjects received sintilimab 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. | 37 |
| nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) Subjects received sintilimab 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. | 21 |
| scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) Subjects received sintilimab 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. | 20 |
| Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) Subjects received sintilimab 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. | 20 |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 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. | 7 |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 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. | 7 |
| Total | 233 |
Baseline characteristics
| Characteristic | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Total | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | Malignant Tumor of the Digestive System or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | MEL: Sintilimab 200mg Q3W (Cohort A) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 44.33 Years STANDARD_DEVIATION 17.01 | 54.54 Years STANDARD_DEVIATION 11.291 | 49.29 Years STANDARD_DEVIATION 11.912 | 62.86 Years STANDARD_DEVIATION 4.14 | 58.20 Years STANDARD_DEVIATION 8.6 | 62.30 Years STANDARD_DEVIATION 6.951 | 60.52 Years STANDARD_DEVIATION 6.539 | 55.35 Years STANDARD_DEVIATION 11.201 | 52.27 Years STANDARD_DEVIATION 11.28 | 49.13 Years STANDARD_DEVIATION 13.061 | 50 Years STANDARD_DEVIATION 16.093 | 48 Years STANDARD_DEVIATION 6.557 | 46 Years STANDARD_DEVIATION 15.524 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 233 Participants | 7 Participants | 7 Participants | 20 Participants | 20 Participants | 21 Participants | 37 Participants | 87 Participants | 22 Participants | 3 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 3 participants | 233 participants | 7 participants | 7 participants | 20 participants | 20 participants | 21 participants | 37 participants | 87 participants | 22 participants | 3 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 61 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants | 6 Participants | 30 Participants | 7 Participants | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 172 Participants | 5 Participants | 6 Participants | 18 Participants | 19 Participants | 16 Participants | 31 Participants | 57 Participants | 15 Participants | 2 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 2 / 3 | 3 / 3 | 1 / 3 | 12 / 22 | 57 / 87 | 25 / 37 | 9 / 21 | 8 / 20 | 3 / 20 | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 18 / 22 | 82 / 87 | 35 / 37 | 19 / 21 | 20 / 20 | 20 / 20 | 7 / 7 | 7 / 7 |
| serious Total, serious adverse events | 1 / 3 | 2 / 3 | 1 / 3 | 1 / 3 | 0 / 22 | 18 / 87 | 11 / 37 | 3 / 21 | 9 / 20 | 6 / 20 | 2 / 7 | 1 / 7 |
Outcome results
Primary
Number of All Study Participants Who Demonstrate a Tumor Response
Time frame: Through out the study (up to 2 years)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Number of All Study Participants Who Demonstrate a Tumor Response | 0 Participants |
| Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Number of All Study Participants Who Demonstrate a Tumor Response | 1 Participants |
| Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Number of All Study Participants Who Demonstrate a Tumor Response | 0 Participants |
| Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | Number of All Study Participants Who Demonstrate a Tumor Response | 1 Participants |
| MEL: Sintilimab 200mg Q3W (Cohort A) | Number of All Study Participants Who Demonstrate a Tumor Response | 1 Participants |
| Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | Number of All Study Participants Who Demonstrate a Tumor Response | 13 Participants |
| NSCLC: Sintilimab 200mg Q3W (Cohort C) | Number of All Study Participants Who Demonstrate a Tumor Response | 5 Participants |
| nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | Number of All Study Participants Who Demonstrate a Tumor Response | 13 Participants |
| scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Number of All Study Participants Who Demonstrate a Tumor Response | 11 Participants |
| Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Number of All Study Participants Who Demonstrate a Tumor Response | 17 Participants |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Number of All Study Participants Who Demonstrate a Tumor Response | 3 Participants |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | Number of All Study Participants Who Demonstrate a Tumor Response | 1 Participants |
Primary
Number of Participants Experiencing Dose-limiting Toxicities (DLTs)
Time frame: Up to 28 days in Cycle 1
Population: All participants in Parts A1 to A4 who received ≥1 dose of study treatment and either 1) had a DLT in Cycle 1 or 2) received ≥90% of the prescribed dose of Sintilimab in Cycle 1 and completed all safety evaluations ≥28 days after the first administration of Sintilimab without experiencing DLT. Per protocol, cohort A to H were not analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Number of Participants Experiencing Dose-limiting Toxicities (DLTs) | 0 Participants |
| Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Number of Participants Experiencing Dose-limiting Toxicities (DLTs) | 0 Participants |
| Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Number of Participants Experiencing Dose-limiting Toxicities (DLTs) | 0 Participants |
| Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | Number of Participants Experiencing Dose-limiting Toxicities (DLTs) | 0 Participants |
Primary
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)
Population: Participants from cohort A to H that received ≥1 dose of study treatment. Per protocol, Part A1 to A4 (dose-escalation) was not analyzed for efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MEL: Sintilimab 200mg Q3W (Cohort A) | Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator | 4.5 percentage of participants |
| Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator | 14.9 percentage of participants |
| NSCLC: Sintilimab 200mg Q3W (Cohort C) | Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator | 13.5 percentage of participants |
| nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator | 61.9 percentage of participants |
| scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator | 55.0 percentage of participants |
| Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator | 85.0 percentage of participants |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator | 42.9 percentage of participants |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator | 14.3 percentage of participants |
Secondary
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
Population: All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available AUC 0-t data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis..
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Area Under the Concentration-time Curve From Zero Time (Predose) to the Time of the Last Measurable Concentration (AUC0-t) | 4800 h*ug/ml | Geometric Coefficient of Variation 8.2 |
| Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Area Under the Concentration-time Curve From Zero Time (Predose) to the Time of the Last Measurable Concentration (AUC0-t) | 12300 h*ug/ml | Geometric Coefficient of Variation 35.2 |
| Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Area Under the Concentration-time Curve From Zero Time (Predose) to the Time of the Last Measurable Concentration (AUC0-t) | 39800 h*ug/ml | Geometric Coefficient of Variation 14.5 |
| Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | Area Under the Concentration-time Curve From Zero Time (Predose) to the Time of the Last Measurable Concentration (AUC0-t) | 10800 h*ug/ml | Geometric Coefficient of Variation 49.3 |
Secondary
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
Population: All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available clearance data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Clearance of IBI308 in Plasma After Single Dose Administration | 8.53 ml/h | Geometric Coefficient of Variation 20.7 |
| Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Clearance of IBI308 in Plasma After Single Dose Administration | 11.7 ml/h | Geometric Coefficient of Variation 33.3 |
| Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Clearance of IBI308 in Plasma After Single Dose Administration | 13.7 ml/h | Geometric Coefficient of Variation 15.9 |
| Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | Clearance of IBI308 in Plasma After Single Dose Administration | 12.9 ml/h | Geometric Coefficient of Variation 61.1 |
Secondary
DOR According to RECIST 1.1 as Assessed by Investigator
Time frame: Through out the study (up to 2 years)
Population: Participants from cohort A to H that received ≥1 dose of study treatment. Per protocol, Part A1 to A4 (dose-escalation) was not analyzed for efficacy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEL: Sintilimab 200mg Q3W (Cohort A) | DOR According to RECIST 1.1 as Assessed by Investigator | NA Days |
| Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | DOR According to RECIST 1.1 as Assessed by Investigator | NA Days |
| NSCLC: Sintilimab 200mg Q3W (Cohort C) | DOR According to RECIST 1.1 as Assessed by Investigator | 368.0 Days |
| nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | DOR According to RECIST 1.1 as Assessed by Investigator | NA Days |
| scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | DOR According to RECIST 1.1 as Assessed by Investigator | 170.5 Days |
| Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | DOR According to RECIST 1.1 as Assessed by Investigator | 181.0 Days |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | DOR According to RECIST 1.1 as Assessed by Investigator | NA Days |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | DOR According to RECIST 1.1 as Assessed by Investigator | NA Days |
Secondary
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
Population: All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available Cmax data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Maximum Concentration (Cmax) of Sintilimab in Solid Tumor Participants | 21.9 ug/ml | Geometric Coefficient of Variation 11.3 |
| Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Maximum Concentration (Cmax) of Sintilimab in Solid Tumor Participants | 69.7 ug/ml | Geometric Coefficient of Variation 12.2 |
| Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Maximum Concentration (Cmax) of Sintilimab in Solid Tumor Participants | 220 ug/ml | Geometric Coefficient of Variation 13.4 |
| Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | Maximum Concentration (Cmax) of Sintilimab in Solid Tumor Participants | 54.6 ug/ml | Geometric Coefficient of Variation 50.5 |
Secondary
OS for Participants
Time frame: Through out the study
Population: Participants from cohort A to H that received ≥1 dose of study treatment. Per protocol, Part A1 to A4 (dose-escalation) was not analyzed for efficacy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEL: Sintilimab 200mg Q3W (Cohort A) | OS for Participants | 518.0 Days |
| Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | OS for Participants | 342.0 Days |
| NSCLC: Sintilimab 200mg Q3W (Cohort C) | OS for Participants | 431.0 Days |
| nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | OS for Participants | 566.0 Days |
| scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | OS for Participants | 461.0 Days |
| Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | OS for Participants | NA Days |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | OS for Participants | NA Days |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | OS for Participants | NA Days |
Secondary
PFS According to RECIST 1.1 as Assessed by Investigator
Time frame: Through out the study (up to 2 years)
Population: Participants from cohort A to H that received ≥1 dose of study treatment. Per protocol, Part A1 to A4 (dose-escalation) was not analyzed for efficacy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEL: Sintilimab 200mg Q3W (Cohort A) | PFS According to RECIST 1.1 as Assessed by Investigator | 62.0 Days |
| Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | PFS According to RECIST 1.1 as Assessed by Investigator | 66.0 Days |
| NSCLC: Sintilimab 200mg Q3W (Cohort C) | PFS According to RECIST 1.1 as Assessed by Investigator | 84.0 Days |
| nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | PFS According to RECIST 1.1 as Assessed by Investigator | 377.0 Days |
| scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | PFS According to RECIST 1.1 as Assessed by Investigator | 194.0 Days |
| Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | PFS According to RECIST 1.1 as Assessed by Investigator | 230.0 Days |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | PFS According to RECIST 1.1 as Assessed by Investigator | NA Days |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | PFS According to RECIST 1.1 as Assessed by Investigator | NA Days |
Secondary
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
Population: All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available T1/2 data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | The Half-life (t1/2) of IBI308 in Plasma After Single Dose Administration | 17 Days | Geometric Coefficient of Variation 7.3 |
| Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | The Half-life (t1/2) of IBI308 in Plasma After Single Dose Administration | 12.7 Days | Geometric Coefficient of Variation 44.6 |
| Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | The Half-life (t1/2) of IBI308 in Plasma After Single Dose Administration | 12.5 Days | Geometric Coefficient of Variation 26.4 |
| Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | The Half-life (t1/2) of IBI308 in Plasma After Single Dose Administration | 16.1 Days | Geometric Coefficient of Variation 32.6 |
Secondary
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
Population: All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available Tmax data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Time to Maximum Concentration (Tmax) of Sintilimab in Solid Tumor Participants | 1.05 hours |
| Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Time to Maximum Concentration (Tmax) of Sintilimab in Solid Tumor Participants | 2.07 hours |
| Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Time to Maximum Concentration (Tmax) of Sintilimab in Solid Tumor Participants | 2.27 hours |
| Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | Time to Maximum Concentration (Tmax) of Sintilimab in Solid Tumor Participants | 1.93 hours |
Secondary
TTR According to RECIST 1.1 as Assessed by Investigator
Time frame: Through out the study (up to 2 years)
Population: Participants from cohort A to H that received ≥1 dose of study treatment. Per protocol, Part A1 to A4 (dose-escalation) was not analyzed for efficacy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MEL: Sintilimab 200mg Q3W (Cohort A) | TTR According to RECIST 1.1 as Assessed by Investigator | 63.0 Days |
| Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | TTR According to RECIST 1.1 as Assessed by Investigator | 64.0 Days |
| NSCLC: Sintilimab 200mg Q3W (Cohort C) | TTR According to RECIST 1.1 as Assessed by Investigator | 63.0 Days |
| nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | TTR According to RECIST 1.1 as Assessed by Investigator | 63.0 Days |
| scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | TTR According to RECIST 1.1 as Assessed by Investigator | 62.0 Days |
| Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | TTR According to RECIST 1.1 as Assessed by Investigator | 63.0 Days |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | TTR According to RECIST 1.1 as Assessed by Investigator | 62.0 Days |
| Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | TTR According to RECIST 1.1 as Assessed by Investigator | 62.0 Days |
Secondary
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
Population: All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available volume of distribution data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Volume of Distribution of IBI308 in Plasma After Single Dose Administration | 5.02 L | Geometric Coefficient of Variation 24 |
| Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Volume of Distribution of IBI308 in Plasma After Single Dose Administration | 5.14 L | Geometric Coefficient of Variation 18.7 |
| Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Volume of Distribution of IBI308 in Plasma After Single Dose Administration | 5.95 L | Geometric Coefficient of Variation 10.5 |
| Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | Volume of Distribution of IBI308 in Plasma After Single Dose Administration | 7.2 L | Geometric Coefficient of Variation 45 |