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

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04162327
• Other study ID #: CIBI315A101
• Status: Completed
• Phase: Phase 1
• Start date: November 26, 2019
• Est. completion date: June 20, 2023

Study information

• Verified date: October 2023
• Source: Innovent Biologics (Suzhou) Co. Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: June 20, 2023
• Est. primary completion date: January 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• IBI315
Patients will receive IBI315 until disease progression, intolerability, informed consent withdraw, or other reasons leading to treatment discontinue.
• IBI315
Patients will receive IBI315 RP2D until disease progression,intolerability, informed consent withdraw, or otherreasons leading to treatment discontinue.

Locations

Country	Name	City	State
China	The 307th Hospital of Chinese People's Liberation Army	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Innovent Biologics (Suzhou) Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluate the efficacy in participants with different expression level of HER2 in tumor tissue		up to 9 months
Other	Evaluate the efficacy in participants with different expression level of PD-L1 in tumor tissue		up to 9 months
Other	Evaluate the efficacy in participants with different expression level of tumor infiltrating lymphocyte (TILs)		up to 9 months
Other	Evaluate the efficacy in participants with different subtype of immune cells in peripheral blood		up to 9 months
Primary	Area under the plasma concentration-time curve (AUC)		up to 9 months
Primary	Maximum plasma concentration (Cmax)		up to 9 months
Primary	Terminal elimination half-life (T1/2)		up to 9 months
Primary	Apparent volume of distribution (Vd)		up to 9 months
Secondary	Evaluate receptor occupancy (RO) following single-dose or multi-dose of IBI315		up to 9 months
Secondary	The percentage of participants with anti-drug antibody (ADA) positive after dosing IBI315		up to 9 months
Secondary	The percentage of participants with neutralizing antibody (NAb) positive after dosing IBI315		up to 9 months