A First-in-human Study of IBI343 in Subjects With Locally Advanced Unresectable or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1a/b, multicenter, open-label, first-in-human, dose escalation, expansion and extension study to evaluate the safety, tolerability, and DLTs to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and preliminary efficacy of IBI343 (study drug) in participants with locally advanced unresectable or metastatic solid tumors.

Official Title
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A Phase 1a/b, Multicenter, Open-label, First-in-human Study of IBI343 in Subjects With Locally Advanced Unresectable or Metastatic Solid Tumors

Conditions
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Locally Advanced Unresectable or Metastatic Solid Tumors

Intervention / Treatment
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* Drug: IBI343


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects, age ≥ 18 years. Phase 1a Dose Escalation: Subjects with a documented (histologically- or cytologically-proven) locally advanced unresectable or metastatic solid tumor malignancy for which standard treatment does not exist, is no longer effective, or is not acceptable to the subject. Phase 1a Dose Expansion and Phase 1b Dose Extension: Subjects with pathologically documented locally advanced unresectable or metastatic gastric/gastro-esophageal junction adenocarcinoma or pancreatic ductal adenocarcinoma with Claudin 18.2 expression. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Adequate bone marrow and organ function. Subjects both male and female, who are either not of childbearing potential or who agree to use two highly effective method of contraception during the study (begin from screening or within 2 weeks prior to the first dose, whichever comes first, and continue until 6 months after the last dose of study drug. Exclusion Criteria: Subjects with a pathologically documented lung cancer. Subjects 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 greater. Subjects 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. Potent cytochrome P450 3A4 (CYP3A4) and/or P450 1A2 (CYP1A2) inhibitors within 2 weeks or 5 half-lives (whichever is longer) before first administration of the study drug. Has adverse reactions resulting from previous antitumor therapies, which have not resolved to Grade 0 or 1 toxicity according to NCI-CTCAE v5.0 (except for alopecia, fatigue, pigmentation and other conditions with no safety risk according to investigators' opinion) or baseline prior to first administration of the study drug. Known symptomatic central nervous system (CNS) metastases. History of pneumonia requiring corticosteroids therapy, or history of clinically significant lung diseases or who are suspected to have these diseases by imaging at screening period Uncontrolled diseases including: Uncontrolled infection requiring systematic antibiotics, antivirals or antifungals within 4 weeks prior to first administration of the study drug; Known human immunodeficiency virus (HIV) infection, or HIV positive (HIV 1/2 Ab positive); HBsAg positive and/or HBcAb positive with HBV DNA titer ≥ 10^4 copies/mL or ≥2000 IU/mL or higher than lower limit of detection) HCV Ab positive with HCV RNA>10^3 copies/mL). Active syphilis infection or latent syphilis requiring treatment; QTc interval > 480 ms SBP≥160mmHg or DBP≥100mmHg History of any arterial thromboembolic event within 6 months prior to the first administration of study drug, including myocardial infarction, unstable angina pectoris, pulmonary embolism, cerebrovascular stroke or transient ischemic attack, etc Risk of intestinal obstruction or perforation (including but not limited to: acute diverticulitis, abdominal abscess, or a history of abdominal cancer) or a history of inflammatory bowel disease or extensive bowel resection (partial colon resection or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.

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: Single arm<br>Phase 1a Dose Escalation: IBI343 will be administered intravenously (IV) at different dose levels following accelerated titration for the first 2 dose levels and traditional 3+3 dose escalation design for following levels. Phase 1a Dose Expansion: IBI343 will be administered at dose levels which is equal or lower than MTD. Each dose level contains no more than 30 subjects (including subjects in dose escalation) Phase 1b Dose Extension: IBI343 will be administered at RP2D. | Drug: IBI343<br>* IBI343 will be administered intravenously (IV) on Day 1 of every 21-day cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Dose-limiting Toxicity (DLT) | 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 IBI343 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum concentration (Cmax) | PK parameters maximum concentration (Cmax) of IBI343 | Up to 2 years | 
| area under the curve (AUC) | PK parameters area under the curve (AUC) of IBI343 | Up to 2 years | 
| clearance rate (CL) | PK parameters clearance rate of IBI343 | Up to 2 years | 
| half-life (t1/2) | PK parameters half-life (t1/2) of IBI343 | Up to 2 years | 
| Anti-drug antibody(ADA) of IBI343 | The incidence and characterization of ADA of IBI343 | Up to 2 years | 
| Objective response rate (ORR) | ORR is defined as the proportion of participants with a complete response (CR) or partial response (PR). | Through study completion, up to 2 years | 
| time to response (TTR) | TTR is defined as the time from the date of first dose of study drug to the date of first documented tumor response (CR/PR). | Through study completion, up to 2 years | 
| duration of response (DoR) | DoR is defined as the time from the date of first documented tumor response (CR/PR) until PD/death. | Through study completion, up to 2 years | 
| disease control rate (DCR) | DCR is defined as the proportion of participants with a complete response (CR) or partial response (PR) or stable disease(SD) | Through study completion, up to 2 years | 
| progression-free survival (PFS) | PFS is defined as the time from the date of first dose of study drug to the date of the first documented progression or death due to any cause, whichever occurs first. | Through study completion, up to 2 years | 
| Overall survival (OS) | OS is defined as the time from the date of first dose of study drug until the date of death from any cause. | through study completion, an average of 1 year | 
| apparent volume of distribution (V) | PK parameters apparent volume of distribution(V) of IBI343 | Up to 2 years |