A Study of IBI129 in Subjects With Unresectable, Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This is a phase 1/2 multicenter, first-in-human study of IBI129. It includes a phase 1 dose escalation and expansion section to identify MTD/RP2D of IBI129, plan to enroll 22 180 subjects, and a phase 2 to explore efficacy, safety and tolerability of IBI129 at RP2D in specified types of solid tumor. Approximately 182 evaluable subjects will be enrolled for phase 2

Official Title
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A Phase 1/2 Study of IBI129 in Subjects With Unresectable, Locally Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: IBI129


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; At least 1 evaluable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.; 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 Exclusion Criteria: Participate in any other interventional clinical research except observational (non-interventional) study or in the follow-up phase of the interventional study; Received previous anti-tumor therapy within 4 weeks or 5 half-lives of the anti-tumor regimens before the first administration of study drug, whichever is shorter. Progressed refractory to an antibody drug conjugate that consists of an exatecan derivative that is a topoisomerase I inhibitor. Plan to receive other antitumor therapy during the study excluding palliative radiotherapy for the purpose of symptom (like pain) relief that must also do not have impact on tumor assessment throughout the study; Known symptomatic central nervous system (CNS) metastases.

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: IBI129<br>IBI129 | Drug: IBI129<br>* Subjects will receive IBI129 on Day 1 of a 21-day cycle (or intervals determined by the Investigator and Sponsor based on safety, toxicity and PK data), until unacceptable toxicity, disease progression, withdrawal of consent, occurrence of other reasons for discontinuing study therapy, or for a maximum of 24 months of treatment, whichever occurs first.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events | Occurrence and severity of adverse events (AEs), with severity determined by NCI CTCAE v5.0 criteria | 24 months | 
| Number of subjects with clinically significant changes in physical examination results | Clinically significant abnormal physical examination findings reported by the investigator. | 24 months | 
| Number of subjects with clinically significant changes in vital signs | Vital signs including body temperature, pulse, respiratory rate, SpO2 and blood pressure | 24 months | 
| MTD or RP2D of IBI129 | Number of subjects with dose-limiting toxicities (DLTs) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration (Cmax) of IBI129 | Plasma concentration of IBI129 for single and multiple doses. | 12 months | 
| Area under the curve (AUC) of IBI129 | AUC of IBI129 for single and multiple doses. | 12 months | 
| Time to maximum concentration (Tmax) of IBI129 | Tmax of IBI129 for single and multiple doses. | 12 months | 
| Clearance (CL) of IBI129 | Clearance of IBI129 from the plasma | 12 months | 
| Volume of distribution (V) of IBI129 | Apparent volume of distribution of IBI129. | 12 months | 
| Half-life (T1/2) of IBI129 | T1/2 of IBI129 for single and multiple doses. | 12 months | 
| Immunogenicity of IBI129 | Incidence of anti-drug (IBI129) antibody | 12 months | 
| Objective response rate (ORR) | ORR as evaluated per the RECIST v1.1 criteria | 24 months | 
| Duration of response (DoR) | DoR as evaluated per the RECIST v1.1 criteria | 24 months | 
| Disease control rate (DCR) | DCR as evaluated per the RECIST v1.1 criteria | 24 months | 
| Time to response (TTR) | TTR as evaluated per the RECIST v1.1 criteria | 24 months | 
| Progression free survival (PFS) | PFS as evaluated per the RECIST v1.1 criteria | 24 months | 
| Overall survival (OS) | Overall survival. | 24 months |