Patient case: 60-year-old male with melanoma; genetic feature: NTRK1 rearrangement

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

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 will expand in 4 participant populations to further evaluate the safety and clinical activity of IBI308 monotherapy or in combination with chemotherapy: Cohort A (monotherapy in participants with advance melanoma), Cohort B (monotherapy in participants with advanced malignancies of the digestive system after failure of at least 1 line of standard therapy), Cohort C (monotherapy in participants with advanced non small cell lung cancer after failure or intolerance of 1st line therapy) and Cohort D (in combination with cisplatin and pemetrexed in treatment naive participants with inoperable locally advanced or advanced non-squamous non small cell lung cancer). 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 will be recorded for up to 28 days after the 1st dose of IBI308. Efficacy will primarily be evaluated by RECIST v1.1. Participants' safety will be monitored throughout the study. Further exploration of pharmacokinetic/pharmacodynamics and immunogenicity information will be assessed throughout the trial.

Eligibility: 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
  -  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

Relevance to patient case: not relevant