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

Launched by INNOVENT BIOLOGICS (SUZHOU) CO. LTD. · Oct 15, 2016

Keywords

ClinConnect Summary

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 carc...

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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