Epidermal Growth Factor Receptor (EGFR) Antagonist Chimeric Anti-EGFR Monoclonal Antibody Trial

NCT03426371 | Terminated Phase 3

• 1 other identifier: KL140-III-01
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

The study is an double blind, randomized, multicenter phase 3 trial. The efficacy analyses are based on 570 Chinese patients with RAS wt mCRC treated with mFOLFOX-6 ± cetuximab. Study treatment continues until disease progression or unacceptable toxicity (ie, not for a fixed number of courses). The primary endpoint of the study is progression-free survival (PFS) time according to RECIST 1.0; key secondary endpoints include overall survival (OS) time, overall response rate (ORR), and safety/tolerability.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Time

  PFS was defined as the duration (in months) from randomization until the first progressive disease (PD) observation as assessed by the investigators according to Response Evaluation Criteria for Solid Tumors (RECIST) version 1.0, or death due to any cause when death occurred within 90 days of randomization or the last tumor assessment, whichever was later. PD was defined as at least a 20% increase in the sum of longest diameter (LD) of the target lesions, taking as references the smallest sum LD since the treatment started (including baseline), or appearance of one or more new lesions, and/or unequivocal progression of existing non-target lesions.

  Time Frame: Baseline up to 128 weeks

Secondary Outcomes (4)

• Overall Survival (OS) Time

  Time Frame: Baseline up to 258 weeks

• Best Overall Response Rate (ORR)

  Time Frame: Baseline up to 128 weeks

• Time to Treatment Failure (TTF)

  Time Frame: Baseline up to 128 weeks

• quality of life score

  Time Frame: Baseline up to 258 weeks

Study Arms (2)

Experimental

EXPERIMENTAL

All eligible subjects will receive KL-140 in combination with mFOLFOX-6 chemotherapy regimen.

Drug: KL-140

Placebo Comparator

PLACEBO COMPARATOR

All eligible subjects will receive Placebo in combination with mFOLFOX-6 chemotherapy regimen.

Drug: Placebo

Interventions

KL-140 DRUG

KL-140 will be administered every 7 days at an initial dose of 400 milligram per square meter (mg/m\^2) at 5 milligram per minute (mg/min) and 250 mg/m\^2 at 10 mg/min for subsequent infusions until progression of disease, withdrawal of consent, or unacceptable toxicity to KL-140. Drug: Oxaliplatin Oxaliplatin 85 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity. Drug: Folinic Acid FA 200 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity. Drug: 5Fluorouracil 5-FU as a bolus of 400 mg/m\^2/day intravenously followed by 2400 mg/m\^2/day infusion over 48 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Experimental

Placebo DRUG

Placebo will be administered every 7 days at an initial dose of 400 milligram per square meter (mg/m\^2) at 5 milligram per minute (mg/min) and 250 mg/m\^2 at 10 mg/min for subsequent infusions until progression of disease, withdrawal of consent, or unacceptable toxicity Drug: Oxaliplatin Oxaliplatin 85 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity. Drug: Folinic Acid FA 200 mg/m\^2 infusion over 120 minutes on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity. Drug: 5Fluorouracil 5-FU as a bolus of 400 mg/m\^2/day intravenously followed by 2400 mg/m\^2/day infusion over 48 hours on Day 1, Day 2, and then every 2 weeks until progression of disease, withdrawal of consent, or unacceptable toxicity.

Placebo Comparator

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Male or female subjects， 18-75 years of age
• Medically accepted effective contraception if procreative potential exists
• Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum
• RAS wild-type and BRAF-V600E wild-type status in tumor tissue
• At least one measurable lesion by computer tomography (CT) or magnetic resonance imaging (MRI) according to RECIST
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at trial entry
• Life expectancy of at least 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at trial entry
• White blood cell count \>= 3 × 10x9/L with neutrophils \>= 1.5 × 10x9/L, platelet count \>=75 × 10x9/L and hemoglobin \>= 8 g/dL； Total bilirubin \<= 1.5 × upper limit of reference range， Aspartate transaminase (AST) and alanine transaminase (ALT) \<= 2.5 × upper limit of reference range or \<= 5 × upper reference range in subjects with liver metastasis；Serum creatinine \<= 1.5 × upper limit of reference range

You may not qualify if:

• Known hypersensitivity or allergic reactions against any of the components of the trial treatments
• Radiotherapy or surgery (excluding prior diagnostic biopsy) in the 28 days before trial treatment
• Known brain metastasis and/or leptomeningeal disease. Subjects with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis
• Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease，except the patient with fistulation or stenting
• Active clinically serious infections (\> grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0), including active tuberculosis
• Uncontrolled diabetes mellitus, pulmonary fibrosis, acute pulmonary disorder, interstitial pneumonia, or liver failure
• Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 5 years, or left ventricular ejection fraction below the institutional range of normal on a baseline multiple gated acquisition scan or echocardiogram
• Renal replacement therapy
• Peripheral neuropathy \> grade 1
• History of organ allograft, autologous stem cell transplantation, or allogeneic stem cell transplantation
• Previous malignancy other than CRC in the last 5 years except basal cell cancer of the skin or preinvasive cancer of the cervix
• Known and declared history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
• Known severe coagulation disorders
• Previous chemotherapy for CRC except adjuvant treatment if terminated \> 12 months (oxaliplatin-based chemotherapy) or \> 6 months (non-oxaliplatin-based chemotherapy) before the start of treatment in this trial
• Previous treatment with anti-EGFR monoclonal antibody therapy

Sponsors & Collaborators

• Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.: lead

Study Sites (1)

307 Hospital of PLA

Beijing, Beijing Municipality, 100071, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: multicenter, double-blind, randomized, controlled phase III trial

Study Record Dates

• First Submitted: January 24, 2018
• First Posted: February 8, 2018
• Study Start: March 18, 2018
• Primary Completion: November 27, 2021
• Study Completion: November 27, 2021
• Last Updated: May 12, 2026

Record last verified: 2026-05

Locations

CN (1)