A Multicentre,Study of IBI133 in Subjects With Unresectable, Locally Advanced or Metastatic Solid Tumours

Study Overview
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Brief Summary
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This is a multicentre, open-label, first-in-human, phase 1/2 study of IBI133 in subjects with unresectable, locally advanced or metastatic solid tumours. Phase 1 section includes three parts, IBI133 dose escalation part, and IBI133 monotherapy dose expansion part. The objective of phase 1 section is to identify MTD/recommended dose for expansion (RDE) of IBI133 monotherapy . The objective of phase 2 section is to further explore efficacy, safety and tolerability of IBI133 monotherapy at RDE in specified tumour population. The treatment cycle of the study is defined as every 3 weeks (21 days).

Official Title
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A Multicentre, Open-label, Phase 1/2 Study of IBI133 in Subjects With Unresectable, Locally Advanced or Metastatic Solid Tumours

Conditions
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Locally Advanced Unresectable or Metastatic Solid Tumors

Intervention / Treatment
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* Biological: IBI133


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol; Male or female subjects ≥ 18 years old; Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1; Anticipated life expectancy of ≥ 12 weeks; Adequate bone marrow and organ function. Has a documented (histologically- or cytologically-proven), unresectable, locally advanced or metastatic solid tumour that is refractory to or intolerable with standard treatment, or for which no standard treatment is available; Exclusion Criteria: Participate in any other interventional clinical research except observational (non-interventional) study or in the follow-up phase of the interventional study; Prior HER3 targeted treatment, including but not limited to monoclonal antibody, bispecific antibody, T cell engager, and antibody-drug conjugate. Prior treatment with an antibody-drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g. DS-8201).

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label：IBI133 monotherapy<br> | Biological: IBI133<br>* IBI133: The provisional dose levels are planned to be evaluated, but it is possible for additional and/or intermediate dose levels to be added during the course of the study. Q3W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities (DLTs) | DLTs are assessed during the DLT observation period to determine maximum tolerated dose (MTD)and /or recommended phase 2 dose (RP2D) | 21 days after the first dose of IBI133 | 
| Safety: Adverse events (AEs);treatment emergent adverse event(TEAEs),serious adverse events(SAEs) | Adverse events will be assessed by investigator(s)according to NCI-CTCAE v5.0 | Up to 90 days after the last administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum concentration (Cmax) | PK parameters maximum concentration(Cmax)of IBI133,total antibody,can will be determined | Up to 2 years | 
| area under the curve (AUC) | PK parameters clearance rate of IBI133,total antibody,exate can will be determined | Up to 2 years | 
| clearance rate(CL) | PK parameters clearance rateof IBI133,total antibody,exate can will be determined | Up to 2 years | 
| half-life (T1/2) | PK parameters half-life of IBI133,total antibody,exate can will be determined | Up to 2 years | 
| anti-drug antibody (ADA) | the incidence and characterization of ADA OF IBI133 will be determined | Up to 2 years | 
| Preliminary efficacy including objective response rate (ORR) | ORR is defined as the proportion of subjects with a CR or PR. Number and percentage of subjects with CR or PR will be summarized. | Through study completion,Up to 2 years | 
| duration of response (DoR) | DoR is defined as the time from the date first achieved CR or PR until the date of first documents disease progression based on RECIST v1.1 or death | Through study completion,Up to 2 years | 
| disease control rate (DCR) | DCR is defined as the proportion of subjects with a CR, PR or SD, and will be analysed in the same fashion as ORR. | Through study completion,Up to 2 years | 
| ,time to response (TTR) | TTR is defined as the time from the date of first study drug to the date first achieved CR or PR based on RECIST v1.1. | Through study completion,Up to 2 years | 
| progression free survival (PFS) | PFS is defined as the time from the date of first study drug to death or disease progression based on RECIST v1.1, whichever occurs first. | Through study completion,Up to 2 years |