Advanced Solid Tumor
Conditions
Brief summary
The primary objective of this phase I study is to evaluate the safety and potential efficacy and to determine the recommended phase 2 dose (RP2D) of IBI315, a HER2/PD-1 bi-specific antibody in patients with advanced solid tumors
Detailed description
This phase Ia/Ib, open-label, multicenter study has two stages. The Ia stage is a dose-escalation study that will focus on safety, tolerability, efficacy and RP2D . Patients with HER2-expressing advanced solid tumor who failed from previous standard of care will be enrolled in the phase Ia study. DLT observation period is 28 days.
Interventions
DRUGIBI315
Patients will receive IBI315 until disease progression, intolerability, informed consent withdraw, or other reasons leading to treatment discontinue.
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Written (signed) informed consent. * Life expectancy ≥12 weeks. * Patients with HER2-expressing advanced solid tumor who failed on current standard of care * According to RECIST 1.1, at least one measurable lesion (radiation-naïve) exists. * ECOG performance status 0-1. * Adequate organ and marrow function evaluated by laboratory tests as follow: * CBC: absolute neutrophil count (ANC) ≥ 1.0×109/L (Ia stage) or 1.5×109/L (Ib stage); Platelet (PLT) ≥ 75×109/L; Hemoglobin (HGB) ≥ 9.0g/L; * Liver function: Total bilirubin (TBIL) ≤ 1.5×upper limit of normal value (ULN) for patients without hepatic metastases, ≤ 2×ULN for patients with hepatic metastases or Gilbert syndrome; Alanine aminotransferase (ALT) ≤ 2.5×ULN; Aspartate transferase (AST) ≤ 2.5×ULN; * Renal function: Clearance of creatinine (CCr) by Cockcroft-Gault formula or 24-hour urine collection ≥ 50ml/min; * Urinalysis: urine protein \< 2+ or urine protein in 24-hour urine collection \< 1g; * Coagulation function: activated partial thromboplastin time (APTT）≤ 1.5×ULN; international normalized ratio (INR）≤ 1.5 * left ventricular ejection fraction (LVEF) ≥ 50% by echocardiography; * Accumulative exposure to doxorubicin ≤ 360mg/m2; accumulative exposure to epirubicin ≤ 720mg/m2; * Agree to use an approved contraceptive method during the treatment period, until 180 days after last dose of treatment. * Post-menopause female subject or pre-menopause female with negative HCG level in urine or blood.
Exclusion criteria
* Any greater than NCI CTCAE 0/1 adverse event exists within 4 weeks before enrollment, not including hair loss and fatigue; * Received major surgery or having unhealed wound, ulcer, or bone fracture;• Received whole pelvic radiation; * Plan to receive any other anti-cancer therapy not specified in the protocol, except for palliative radiotherapy; * CNS metastasis, spinal compression, or carcinomatous meningitis * Active autoimmune disease or inflammatory disorders. * Primary immunodeficiency diseases; * Pregnant or breast-feeding female.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Apparent volume of distribution (Vd) | up to 9 months |
| Area under the plasma concentration-time curve (AUC) | up to 9 months |
| Terminal elimination half-life (T1/2) | up to 9 months |
| Maximum plasma concentration (Cmax) | up to 9 months |
Secondary
| Measure | Time frame |
|---|---|
| The percentage of participants with neutralizing antibody (NAb) positive after dosing IBI315 | up to 9 months |
| The percentage of participants with anti-drug antibody (ADA) positive after dosing IBI315 | up to 9 months |
| Evaluate receptor occupancy (RO) following single-dose or multi-dose of IBI315 | up to 9 months |
Other
| Measure | Time frame |
|---|---|
| Evaluate the efficacy in participants with different expression level of HER2 in tumor tissue | up to 9 months |
| Evaluate the efficacy in participants with different subtype of immune cells in peripheral blood | up to 9 months |
| Evaluate the efficacy in participants with different expression level of tumor infiltrating lymphocyte (TILs) | up to 9 months |
| Evaluate the efficacy in participants with different expression level of PD-L1 in tumor tissue | up to 9 months |
Countries
China
Outcome results
None listed