A Phase Ia/Ib Study of IBI315 in Patients With HER2-expressing Advanced Solid Tumor

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase Ia/Ib, Open-label, Multicenter, Dose-escalation Study Evaluating the Safety, Tolerability, and Potential Efficacy of IBI315, an Anti-HER2/PD-1 Bi-specific Antibody in Patients With HER2-expressing Advanced Solid Tumor

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: IBI315
* Drug: IBI315


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ia stage - IBI315 Dose escalation<br> | Drug: IBI315<br>* Patients will receive IBI315 until disease progression, intolerability, informed consent withdraw, or other reasons leading to treatment discontinue.<br>|
| Experimental: Ib stage - IBI315 monotherapy<br> | Drug: IBI315<br>* Patients will receive IBI315 RP2D until disease progression,intolerability, informed consent withdraw, or otherreasons leading to treatment discontinue.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve (AUC) |  | up to 9 months | 
| Maximum plasma concentration (Cmax) |  | up to 9 months | 
| Terminal elimination half-life (T1/2) |  | up to 9 months | 
| Apparent volume of distribution (Vd) |  | up to 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate receptor occupancy (RO) following single-dose or multi-dose of IBI315 |  | up to 9 months | 
| The percentage of participants with anti-drug antibody (ADA) positive after dosing IBI315 |  | up to 9 months | 
| The percentage of participants with neutralizing antibody (NAb) positive after dosing IBI315 |  | up to 9 months |