KN026 in Combination With Chemotherapy in HER2 Positive Gastric Cancer Subjects Who Have Failed First-line Therapy

NCT05427383 | Recruiting Phase 2 DMC

• 1 other identifier: KN026-001
• Study Type: interventional
• Target: 286
• Locations: 1 country
• Sites: 1

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.

Conditions

Stomach Cancer

Keywords

Stomach Neoplasm; Gastric Cancer; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS) according to RECIST 1.1 by IRC

  The time from the first dose of study treatment to the date of documented disease

  Up to 2.5 years

• Overall Survival (OS) according to RECIST 1.1 by IRC

  The time from the first dose of study treatment until the date of death from any cause

  Up to 2.5 years

Secondary Outcomes (8)

• ORR according to RECIST 1.1 by Investigator's Assessment and IRC

  Up to 2.5 years

• DCR according to RECIST 1.1 by Investigator's Assessment and IRC

  Up to 2.5 years

• DOR according to RECIST 1.1 by Investigator's Assessment and IRC

  Up to 2.5 years

• Progression Free Survival (PFS) according to RECIST 1.1 by Investigator's Assessment

  Up to 2.5 years

• Frequency and Severity of Adverse Events according to NCI CTCAE 5.0

  Up to 2.5 years

Other Outcomes (7)

• To explore the correlation of gene mutation status and the efficacy

  Up to 2.5 years

• Subjects will be assessed using the European Quality of Life 5 Dimensions and 5 Lines (EQ-5D-5L) scales

  Up to 2.5 years

• Subjects will be assessed using the Quality of Life Questionnaire-Core 30 (QLQ-C30) scales

  Up to 2.5 years

Study Arms (2)

KN026 + Paclitaxel/ Docetaxel/ Irinotecan

EXPERIMENTAL

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; Drug: Paclitaxel Injection; Drug: Docetaxel Injection; Drug: Irinotecan Injection

Placebo + Paclitaxel/ Docetaxel/ Irinotecan

EXPERIMENTAL

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; Drug: Paclitaxel Injection; Drug: Docetaxel Injection; Drug: Irinotecan Injection

Interventions

KN026/Placbo Injection DRUG

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

KN026 + Paclitaxel/ Docetaxel/ Irinotecan; Placebo + Paclitaxel/ Docetaxel/ Irinotecan

Paclitaxel Injection DRUG

IV Paclitaxel at 175 mg/m² on D1, Q3W

KN026 + Paclitaxel/ Docetaxel/ Irinotecan; Placebo + Paclitaxel/ Docetaxel/ Irinotecan

Docetaxel Injection DRUG

IV Docetaxel at 75 mg/m² on D1, Q3W

KN026 + Paclitaxel/ Docetaxel/ Irinotecan; Placebo + Paclitaxel/ Docetaxel/ Irinotecan

Irinotecan Injection DRUG

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

KN026 + Paclitaxel/ Docetaxel/ Irinotecan; Placebo + Paclitaxel/ Docetaxel/ Irinotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years;
• Histologically or cytology-confirmed HER2-positive locally advanced, recurrent, or metastatic gastric cancer (including adenocarcinoma of the gastro-esophageal junction); HER2 positive is defined as IHC 3+, or IHC 2+ with ISH test positive (HER2/CEP17 ratio ≥ 2.0, or mean HER2 copy number ≥ 6.0 signals/cell);
• Failure of at least first-line standard therapy (trastuzumab plus chemotherapy); Note: Neoadjuvant/adjuvant therapy previously administered with a trastuzumab-containing regimen can be considered first-line therapy if the subject has progressed disease during neoadjuvant/adjuvant therapy or within 6 months of completion of treatment;
• Stage 1 : At least one measurable lesion at baseline according to RECIST 1.1; Stage 2: At least one evaluable lesion at baseline according to RECIST 1.1; the area must not have received previous radiotherapy, or there must be evidence of significant progression after the end of radiotherapy;
• ECOG Performance Status of 0 to 1.
• Life expectancy ≥ 3 months.
• \. The function of major organs must meet the following criteria : Hemoglobin (Hb) ≥ 90 g/L; Absolute neutrophil (ANC) ≥ 1.5×10\^9/L; Platelet (PLT) ≥ 90×10\^9/L; (No whole blood or component blood transfusion in the last 14 days; no pro-hematopoietic cytokines used in the last 7 days); AST, ALT ≤2.5× ULN (upper limit of normal value) (if liver metastases, AST, ALT ≤5×ULN); Total bilirubin (TBIL) ≤1.5×ULN; Albumin≥ 28 g/L; creatinine clearance ≥ 50 mL/min (standard Cockcroft-Gault formula applied); Activated partial thromboplastin time (APTT) ≤ 1.5×ULN, international normalized ratio (INR)/or prothrombin time (PT) ≤ 1.5×ULN; (It is allowed to receive anticoagulants at low stable doses, eg at a dose of aspirin 100 mg/day);
• Left ventricular ejection fraction (LVEF) ≥ 50% or lower limit of normal (LLN) in local sites, measured by echocardiography (ECHO), cardiac radionuclide scanning (MUGA) only in the absence of ECHO, with consistency at baseline and follow-up measurements;
• Subjects agreed to use effective contraception during the study and for 6 months after the last dose (women of childbearing age must confirm a negative serum pregnancy test within 7 days prior to enrollment);
• 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.)
• Subjects are able and willing to comply with the study protocol.

You may not qualify if:

• Subjects with untreated active brain metastases; Subjects will be admitted if their brain metastases have been treated and the metastases are stable (brain imaging at least 4 weeks prior to the first dose showed stable lesions with no new CNS symptoms, or CNS symptoms have returned to baseline and no hormonal therapy is required at least 14 days prior to the first dose of the investigational treatment), and there is no evidence of new or enlarged original brain metastases;
• Other investigational medications received within 4 weeks prior to the first study treatment, based on the time of the last trial dose;
• Antineoplastic therapy such as chemotherapy, small molecule inhibitors, immunotherapy (such as interleukin, interferon, or thymosin) within 4 weeks or 5 half-lives (whichever is shorter but at least 2 weeks) prior to the first study treatment; Have received Chinese herbal treatment with antitumor activity within 14 days before administration;
• Subjects recieved major surgery (e.g., transabdominal, transthoracic, etc.) within 28 days prior to the first study treatment; does not include minor procedures such as diagnostic puncture or infusion device implantation), or major surgery is expected to be required during the study;
• Previous cumulative doses of doxorubicin exceeding 320 mg/m\^2, or equivalent conversion of other anthracyclines (anthracycline equivalent: 1 mg doxorubicin = 2 mg epirubicin = 2 mg pyrrubicin = 2 mg daunorubicin = 0.5 mg normethoxydaunorubicin = 0.45 mg mitoxantrone; except doxorubicin liposomes);
• Previous use of anti-HER2 therapy other than trastuzumab (eg, ADC, dual-antibody, small molecule targeted therapy, etc.).
• Pregnant or lactating women; or intend pregnancy during the trial or within 6 months of the end of the trial;
• Subjects with a history of life-threatening allergies or known allergies to protein drugs or recombinant proteins or to one of excipients in KN026 drugs (histidine, glacial acetic acid, sucrose, and polysorbate 20) who have had a severe hypersensitivity reaction to trastuzumab.
• Adverse events have not returned to CTCAE 5.0 grade ≤ grade 1 or baseline from previous anti-tumor treatments , except for alopecia, skin pigmentation and those assessed by the investigators without potential safety risk.
• Uncontrollable diarrhoea (≥grade 2 that does not improve within 48 hours of medication);
• Subjects with the following history of cardiovascular disease:
• Subjects with uncontrolled hypertension (defined as sustained systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg despite antihypertensive medication);
• Any history of symptomatic congestive heart failure (NYHA classification II-IV); the absolute value of LVEF decreased by ≥10% and absolute value \< 50% , or the absolute value of LVEF decreased by ≥15% , during or after treatment with trastuzumab or other anti-HER2 treatment;
• History of myocardial infarction within 6 months before treatment of the first dose;
• Subjects with angina and unstable angina within three months prior to treatment in the first dose;

Sponsors & Collaborators

• Shanghai JMT-Bio Inc.: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Paclitaxel; Docetaxel; Irinotecan

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2022
• First Posted: June 22, 2022
• Study Start: April 7, 2022
• Primary Completion: November 1, 2025
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 19, 2023

Record last verified: 2023-12

Locations

CN (1)