KN026 in Combination With Chemotherapy in the Second Line Treatment of HER-2 Positive Advanced or Metastatic Gastric Cancer

Sponsor

Shanghai JMT-Bio Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05427383

Collaborator

(none)

286

Enrollment

Location

Arms

54.8

Anticipated Duration (Months)

5.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

KN026-001 is a two-stage study (Open-label stage/Randomized stage). Open-label stage is designed to evaluate the safety and efficacy of KN026 and chemotherapy when given together. Randomized stage is designed to evaluate the OS and PFS in patients receiving KN026 and chemotherapy compared to patients receiving placebo and chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Stomach Cancer	Drug: KN026/Placbo Injection Drug: Paclitaxel Injection Drug: Docetaxel Injection Drug: Irinotecan Injection	Phase 2/Phase 3

Detailed Description

This is a two-stage study in patients with HER2-positive, unresectable or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma who have progressed on or after a trastuzumab-containing regimen. Stage 1 is an open-label, multicenter, phase II study of KN026 and paclitaxel or irinotecan when given together. Once the safety and efficacy have been established in Stage 1, patients will be enrolled into Stage 2. Stage 2 is a randomized, multicenter, phase III study designed to evaluate the OS and PFS in patients receiving KN026 and chemotherapy compared to patients receiving placebo and chemotherapy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

286 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

An Randomized, Multicenter, Double-Blind, Phase Ⅱ/Ⅲ Study of KN026 in Combination With Chemotherapy Versus Chemotherapy Alone in the Second Line Treatment of HER-2 Positive Advanced or Metastatic Gastric Cancer

Actual Study Start Date :

Apr 7, 2022

Anticipated Primary Completion Date :

Nov 1, 2025

Anticipated Study Completion Date :

Nov 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KN026 + Paclitaxel/ Docetaxel/ Irinotecan IV KN026 at 30 mg/kg on D1 and IV Paclitaxel at 175 mg/m² on D1 or IV Docetaxel at 75 mg/m² on D1 or IV Irinotecan at 125 mg/m² on D1, D8, Q3W	Drug: KN026/Placbo Injection IV KN026/Placebo at 30 mg/kg on D1, Q3W Drug: Paclitaxel Injection IV Paclitaxel at 175 mg/m² on D1, Q3W Drug: Docetaxel Injection IV Docetaxel at 75 mg/m² on D1, Q3W Drug: Irinotecan Injection IV Irinotecan at 125 mg/m² on D1, D8, Q3W
Experimental: Placebo + Paclitaxel/ Docetaxel/ Irinotecan IV Placebo at 30 mg/kg on D1 and IV Paclitaxel at 175 mg/m² on D1 or IV Docetaxel at 75 mg/m² on D1 or IV Irinotecan at 125 mg/m² on D1, D8, Q3W	Drug: KN026/Placbo Injection IV KN026/Placebo at 30 mg/kg on D1, Q3W Drug: Paclitaxel Injection IV Paclitaxel at 175 mg/m² on D1, Q3W Drug: Docetaxel Injection IV Docetaxel at 75 mg/m² on D1, Q3W Drug: Irinotecan Injection IV Irinotecan at 125 mg/m² on D1, D8, Q3W

Arm

Intervention/Treatment

Experimental: KN026 + Paclitaxel/ Docetaxel/ Irinotecan

IV KN026 at 30 mg/kg on D1 and IV Paclitaxel at 175 mg/m² on D1 or IV Docetaxel at 75 mg/m² on D1 or IV Irinotecan at 125 mg/m² on D1, D8, Q3W

Drug: KN026/Placbo Injection

IV KN026/Placebo at 30 mg/kg on D1, Q3W

Drug: Paclitaxel Injection

IV Paclitaxel at 175 mg/m² on D1, Q3W

Drug: Docetaxel Injection

IV Docetaxel at 75 mg/m² on D1, Q3W

Drug: Irinotecan Injection

IV Irinotecan at 125 mg/m² on D1, D8, Q3W

Experimental: Placebo + Paclitaxel/ Docetaxel/ Irinotecan

IV Placebo at 30 mg/kg on D1 and IV Paclitaxel at 175 mg/m² on D1 or IV Docetaxel at 75 mg/m² on D1 or IV Irinotecan at 125 mg/m² on D1, D8, Q3W

Drug: KN026/Placbo Injection

IV KN026/Placebo at 30 mg/kg on D1, Q3W

Drug: Paclitaxel Injection

IV Paclitaxel at 175 mg/m² on D1, Q3W

Drug: Docetaxel Injection

IV Docetaxel at 75 mg/m² on D1, Q3W

Drug: Irinotecan Injection

IV Irinotecan at 125 mg/m² on D1, D8, Q3W

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) according to RECIST 1.1 by IRC [Up to 2.5 years]
The time from the first dose of study treatment to the date of documented disease
Overall Survival (OS) according to RECIST 1.1 by IRC [Up to 2.5 years]
The time from the first dose of study treatment until the date of death from any cause

Secondary Outcome Measures

ORR according to RECIST 1.1 by Investigator's Assessment and IRC [Up to 2.5 years]
The percentage of patients with a complete response (CR) or partial response (PR)
DCR according to RECIST 1.1 by Investigator's Assessment and IRC [Up to 2.5 years]
Number of subjects who achieved a best response of CR, PR, or SD during treatment
DOR according to RECIST 1.1 by Investigator's Assessment and IRC [Up to 2.5 years]
The time from the first objective response (CR or PR) to documented PD, clinical progression, or death from any cause
Frequency and Severity of Adverse Events according to NCI CTCAE 5.0 [Up to 2.5 years]
Number of participants with treatment-related adverse events as assessed by CTCAE 5.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years, regardless of gender.
Unresectable locally advanced, recurrent or metastatic gastric cancer (including gastric-esophageal junction adenocarcinoma) confirmed by histopathology and/or cytology; HER2 positive expression is defined as IHC 3+ or IHC 2+ with ISH test positive.
Stage 1: Progression on or after≥1st -line treatment for gastric carcinoma. Stage 2: Progression on or after 1st -line treatment alone for gastric carcinoma.

(The standard 1st-line therapy must have contained trastuzumab or trastuzumab analog and platinum-based regimen and/or 5-fluoropyrimidine.)

Stage 1: At least one measurable lesion at baseline according to RECIST v1.1. Stage 2: At least one evaluable lesion at baseline according to RECIST v1.1.
ECOG Performance Status of 0 to 1.
Life expectancy ≥ 3 months.
The function of major organs must meet the following criteria within 7 days before enrollment (Have not received blood transfusion within 14 days before the first dose of study drug, have not received hematopoietic cytokines within 7 days before the first dose of study drug):

Absolute neutrophil count (ANC) ≥1.5×10^{9 /L; Platelet ≥90×10}9/L; Hemoglobin ≥90 g/L; Total bilirubin ≤1.5×Upper Limit of Normal (ULN) and Direct bilirubin ≤1.0×ULN; Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5×ULN, or ≤5×ULN for patient with liver metastasis; Albumin ≥28g /L; Creatinine Clearance Rate ≥30 mL/min (Calculated by Cockcroft-Gualt formula); Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN; International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN.

Left ventricular ejection fraction (LVEF) ≥50% or Lower Limit of Normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive.
New York Heart Association (NYHA) heart function classification is level 0 or Ⅰ.
Female and male patient of childbearing age must agree to take adequate contraceptive measures during the entire study period and through at least 6 months after the last dose of study drug. (Women of childbearing age must have a negative pregnancy test prior to study entry.)
Volunteer to participate in this study and sign the informed consent form.
Willingness and able to understand and comply with the requirements of the study.

Exclusion Criteria:

Patients with untreated active brain metastasis; patients are allowed to be enrolled if brain metastasis have been treated and the condition is stable without evidence of new metastasis or enlargement of primary metastasis.
Patients have received other clinical trial drugs before the first dose of study drug within 4 weeks.
Accepted any other anti-tumor drug therapies before the first dose of study drug within 4 weeks or 5 half-lives, whichever is shorter but at least 2 weeks. Accepted Chinese medicine treatment with anti-tumor indications within 2 weeks.
Accepted radiotherapy within 2 weeks before the first dose of study drug. Or has not recovered from all acute toxicity, requires steroid treatment, or has radioactive pneumonia.
Accepted major surgery within 4 weeks before the first dose of study drug. Or expected to require major surgery during the study.
An anthracyclines antibiotic treatment, such as doxorubicin (Adriamycin) was received exceeding 320 mg/m², or other equivalent dose anthracyclines.
Pregnant or nursing females; or intend pregnancy within this study period or within 6 months after the end of this study.
Patients with history of life-threatening allergies or allergy to any components (trastuzumab analogues, MMAE, sodium citrate dihydrate, citric acid monohydrate, polysorbate 20, sucrose, etc.) of KN026.
Has not recovered from adverse reactions caused by previous anti-tumor treatments to ≤ grade 1 or baseline (refer to NCI CTCAE 5.0), except for alopecia and skin pigmentation (any grade is allowed) (peripheral neuropathy > grade 1 cannot be included).
Uncontrollable diarrhea. (eg. water-like stools, uncontrollable after medication, ≥2 grade, defecation times ≥5 times/day).
Patients with the following cardiac function defects at the time of enrollment:

Poorly controlled hypertension (systolic BP>150 mmHg and/or diastolic BP>100 mmHg);
A confirmed history of heart failure (NYHA classification II-IV); during trastuzumab or other anti-HER2 treatment, or after treatment, the absolute value of LVEF decreased by ≥10% and absolute value < 50%, or the absolute value of LVEF decreased by ≥15%.
Myocardial infarction < 6 months before first dose;
Angina, or unstable angina < 3 months before first dose;
Severe arrhythmias and conduction abnormalities (except atrial fibrillation and paroxysmal supraventricular tachycardia) requiring antiarrhythmic therapy other than beta-blockers or digoxin < 6 months before first dose.
QT interval corrected by Fridericia formula prolongation (male>450ms, female>470ms);
Other serious heart problems judged significant clinical significance by the investigator.

Systemic diseases, including diabetes, pulmonary fibrosis, acute lung diseases (except radioactive pneumonia), which are poorly controlled as determined by the investigator.
Severe chronic and active infection, need system antibiosis/antiviral treatment.
Any conditions requiring corticosteroids (> 10 mg per day of prednisone or equivalent) as systemic treatment within 2 weeks before first dose. Allowing subjects to use local and inhaled glucocorticoid therapy.
History of (non-infectious) interstitial pneumonia, or pulmonary disease that requires steroid treatment.
History of immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disease, or a history of organ transplantation.
Patients with active hepatitis B or C, or HIV positive, or syphilis antibody positive (confirmed).
History of any other malignant tumors within five years (except for skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, local prostate cancer, cervical cancer in situ and breast cancer in situ).
Cavity effusion (pleural effusion, ascites, pericardial effusion, etc.) requiring drainage or diuretic treatment within 2 weeks before enrollment. Diuretics are permitted for other reasons.
Even with peripheral or central venous nutritional support, unintentional weight loss ≥5% within 1 month before the first dose.
Inability to tolerate or refuse chemotherapy required by the protocol.
According to the judgment of the investigator, patients are unfit to participate in the clinical study due to any clinical or laboratory abnormalities or a history of systemic disease or other reasons.