A Phase Ia/Ib Study of IBI315 in Patients With HER2-expressing Advanced Solid Tumor
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ia stage - IBI315 Dose escalation
|
Drug: IBI315
Patients will receive IBI315 until disease progression, intolerability, informed consent withdraw, or other reasons leading to treatment discontinue.
|
| Experimental: Ib stage - IBI315 monotherapy
|
Drug: IBI315
Patients will receive IBI315 RP2D until disease progression,intolerability, informed consent withdraw, or otherreasons leading to treatment discontinue.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Other Outcome Measures
- 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 expression level of PD-L1 in tumor tissue [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 subtype of immune cells in peripheral blood [up to 9 months]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The 307th Hospital of Chinese People's Liberation Army | Beijing | China |
Sponsors and Collaborators
- Innovent Biologics (Suzhou) Co. Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CIBI315A101