Phase 2 Study of KH903 in Patients With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma As Second-Line Therapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of the study drug known as KH903 in participants with gastric and gastroesophageal cance

Official Title
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A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 2 Study of Weekly Paclitaxel With or Without KH903 in Patients With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma, Refractory to or Progressive After First-Line Therapy With Platinum and Fluoropyrimidine

Conditions
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Gastric Cancer, Gastroesophageal Cancer

Intervention / Treatment
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* Drug: KH903 + Paclitaxel
* Drug: Placebo + Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Prior to any detailed procedures of this study, subjects are able to understand, voluntarily participate in and sign the informed consent approved by the ethics committee. 2.Age ≥ 18 years. 3.Histologically confirmed, unresectable, locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma . 4.Have at least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1. 5.Have experienced documented objective radiographic or symptomatic disease progression during first-line therapy, or within 4 months after the last dose of first-line therapy with any platinum or/and fluoropyrimidine doublet for unresectable or metastatic disease.Second line chemotherapy is suitable for paclitaxel. 6.Laboratory test values must meet the following criteria. ANC ≥1.5×109/L, platelets ≥ 100×109/L, hemoglobin≥9g/dL. Blood creatinine ≤ 1.5 ×ULN or creatinine clearance ≥ 50 mL/min/m2. Total bilirubin ≤ 1.5× ULN(≤ 3 x ULN if Gilbert disease), AST and ALT ≤ 2.5× ULN (≤ 5×ULN if hepatic metastasis). INR ≤ 1.5× ULN, APTT ≤ 1.5× ULN. Dipstick proteinuria <2+ or 24 hour proteinuria <1g . 7.Good performance status Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1. 8.Life expectancy of ≥ 3 months. Exclusion Criteria: 1.Histologically confirmed squamous cell carcinoma or undifferentiated gastric cancer. 2.Patients with disease progression within 6 months after previous adjuvant or neoadjuvant chemotherapy with paclitaxel, or patients with recurrent or metastatic gastric adenocarcinoma or GEJ adenocarcinoma treated with paclitaxel. 3. GI perforation and/or fistulae in the 6 months preceding randomization. 4.Deep-vein thrombosis, pulmonary embolism (PE), or any other episode of Uncontrolled thromboembolism in the 6 months preceding randomization. 5.Any arterial thromboembolic event (such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack) 6.Uncontrolled hypertension (≥150/100 mm Hg ) despite properly observed antihypertensive therapy. 7.Known brain metastasis. 8.Known allergy to paclitaxel or KH903. 9.Serious concurrent infection or medical illness. 10.Active hepatitis B virus or Active hepatitis C virus (HCV) infection at screening. 11.Any condition which results in an undue risk for the patient during the trial participation according to the investigator.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KH903 + Paclitaxel<br>IV KH903 4 mg/kg IV paclitaxel 80 mg/m² | Drug: KH903 + Paclitaxel<br>* KH903 4 mg/kg will be administered intravenously on D1 D8 D15and D22 in a 28-day cycle； Paclitaxel 80 mg/m² will be administered intravenously on D1, D8 and D15 in a 28-day cycle<br>|
| Active Comparator: Placebo + Paclitaxel<br>IV Placebo IV paclitaxel 80 mg/m² | Drug: Placebo + Paclitaxel<br>* Placebo will be administered intravenously on D1 D8 D15and D22 in a 28-day cycle； Paclitaxel 80 mg/m² will be administered intravenously on D1, D8 and D15 in a 28-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival（PFS） | Date of randomization until the date of first documented Progression or date of death from any cause， whichever came first | Time from date of randomization until the date of first documented Progression or date of death from any cause， whichever came frist，assessed up to18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Percentage of Participants with a Best Overall Response (BOR) of Partial Response (PR) or Complete Response (CR) | Time from date of randomization until the date of first documented CR or PR，assessed up to18 months | 
| Duration of Response (DOR) | is defined as the time from first documented evidence of CR or PR until the date of first documented progression as assessed by RECIST 1.1 or death; assessed up to18 months | Time from first documented evidence of CR or PR until the date of first documented progression ，assessed up to18 months | 
| Disease Control Rate (DCR) | Percentage of Participants who have achieved CR, PR and SD to study treatment; | Time from date of randomization until the date of first documented Progression，assessed up to18 months | 
| AE | Number of Subjects with treatment-related adverse events (AEs)Defined by all | AEs（NCI CTCAE 5.0） collected at each cycle，Assessed up to18 months |