First in Human Study of IBI308 in Chinese Subjects With Advanced Solid Tumors
Condition: Cancer, Solid Tumor
MeSH terms: Neoplasms
Intervention: IBI308; IBI308\Cisplatinum\Pemetrexed; IBI308\cisplatin\gemcitabine; IBI308\oxaliplatin\capecitabine; IBI308\etoposide\cisplatin; IBI308\irinotecan\5-FU
Intervention MeSH terms: Cisplatin; Gemcitabine; Capecitabine; Oxaliplatin; Irinotecan; Etoposide; Pemetrexed
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 233.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

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.
    

Eligibility 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