An Open-label, Phase 1 Study to Determine the Maximum Tolerated Dose of HLX07,in Patients With Advanced Solid Cancers

NCT02648490 | Completed Phase 1

• 1 other identifier: HLX07FIH
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 2

Brief Summary

This study is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of humanized anti-EGFR monoclonal antibody, HLX07, in patients with epithelial cancer who have failed standard therapy and deemed unamenable by conventional therapy. This study will also evaluate the pharmacokinetics, pharmacodynamics, immunogenicity and anti-tumor effect of HLX07 and explore the potential prognostic and predictive biomarkers.

Conditions

Solid Tumour

Keywords

metastatic or recurrent epithelial cancer

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  1 year

Secondary Outcomes (1)

• Number of participants with treatment-related pathological Complete Response assessed using RECIST 1.1 criteria.

  1 year

Study Arms (1)

HLX07, in patients with solid cancers.

EXPERIMENTAL

Each cycle of treatment consists of 4 weeks. Patients who enroll into this study will receive weekly infusion of assigned dose of HLX07. No intra-patient dose escalation is allowed.The proposed dose escalation sequence is 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg. Acetaminophen 500 mg PO 30 minutes before the infusion of HLX07, followed by dexamethasone 10 mg intravenous infusion for 10 minutes, and followed by diphenhydramine 30 mg intravenous infusion for 10 minutes. If the patient experience grade 2 or 3 nausea and vomiting during the first infusion of HLX07, the addition of 5-HT3 inhibitor may be included in the premedication before subsequent infusions.

Drug: HLX07; Drug: Acetaminophen; Drug: dexamethasone; Drug: diphenhydramine; Drug: 5-HT3 inhibitor

Interventions

HLX07 DRUG

recombinant human anti-EGFR monoclonal antibody against cancers

Also known as: anti-EGFR monoclonal antibody

HLX07, in patients with solid cancers.

Acetaminophen DRUG

Acetaminophen 500 mg PO 30 minutes before the infusion of HLX07.

Also known as: Tylenol

HLX07, in patients with solid cancers.

dexamethasone DRUG

dexamethasone 10 mg intravenous infusion for 10 minutes before the infusion of HLX07.

Also known as: Decadron, Dexasone

HLX07, in patients with solid cancers.

diphenhydramine DRUG

diphenhydramine 30 mg intravenous infusion for 10 minutes before the infusion of HLX07.

Also known as: Allermax, Benadryl

HLX07, in patients with solid cancers.

5-HT3 inhibitor DRUG

If the patient experience grade 2 or 3 nausea and vomiting during the first infusion of HLX07, the addition of 5-HT3 inhibitor may be included in the premedication before subsequent infusions.

Also known as: Ondansetron

HLX07, in patients with solid cancers.

Eligibility Criteria

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

You may qualify if:

• Histologically-confirmed, unidimensionally-measurable and/or evaluable carcinoma which has failed standard therapy or for whom no standard therapy is available.
• ECOG performance status score of ≤ 2 at study entry.
• Able to provide written informed consent.
• White blood cell (WBC) count ≥3 x 109/L;an absolute neutrophil count ≥ 1.5 x 109/L;a hemoglobin level \> 90 g/L; and a platelet count ≥ 100 x 109/L.
• Adequate hepatic function as defined by: alkaline phosphatase level ≤ 5.0 x the ULN, bilirubin level ≤ 1.5 x the ULN, aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5 x the ULN or ≤ 5 x the ULN for patients with liver metastases
• Adequate renal function as defined by a serum creatinine level within normal limits.
• Use of effective contraception if procreative potential exists.
• Life expectancy of approximately 3 months or longer in the opinion of the investigator.

You may not qualify if:

• Chemotherapy, radiation, and/or hormonal therapy (except palliative radiation therapy for disease-related pain and chronic hormonal therapy for prostate carcinoma) within 4 weeks of study entry.
• Concurrent unstable or uncontrolled medical disease (e.g., active uncontrolled systemic infection, poorly controlled hypertension or history of poor compliance with an anti-hypertensive regimen, unstable angina, congestive heart failure, uncontrolled diabetes) or other chronic disease, which, in the opinion of the investigator, could compromise the patient or the study.
• Newly-diagnosed or symptomatic brain metastases (patients with a history of brain metastases must have received definitive surgery or radiotherapy, be clinically stable, and not taking steroids; anticonvulsants are allowed).
• Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for more than 3 years will be allowed to enter the trial.
• Any condition that prevents the patient from providing informed consent.
• Pregnancy (confirmed by serum beta human chorionic gonadotropin \[beta-HCG\]) or breast-feeding.
• Any investigational agent(s) or device(s) within 4 weeks of study entry.
• Prior treatment with cetuximab, or any other anti-EGFR monoclonal antibody therapy for less than 3 months. Prior treatment with other monoclonal antibodies targeting receptors other than the EGFR is permitted if the drug has been discontinued more than (include) 4 weeks prior to study entry.
• Tumor cells with either K-ras, N-ras or B-raf mutations.
• Known history of human immunodeficiency virus infection.
• Employees of the investigator or study center with direct involvement in this study or other studies under the direction of the investigator or study center, as well as family members of the employees.

Sponsors & Collaborators

• Henlix, Inc: lead

Study Sites (2)

Henlix, Inc.

Fremont, California, 94538, United States

Location

Linkou Chang Gung Memorial Hospital

Taoyuan District, Taiwan

Location

Related Publications (1)

• Hou MM, Ho CL, Lin HY, Zhu Y, Zhang X. Phase I first-in-human study of HLX07, a novel and improved recombinant anti-EGFR humanized monoclonal antibody, in patients with advanced solid cancers. Invest New Drugs. 2021 Oct;39(5):1315-1323. doi: 10.1007/s10637-021-01099-1. Epub 2021 Mar 13.

  PMID: 33713216 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

HLX07; Acetaminophen; Dexamethasone; Calcium Dobesilate; Diphenhydramine; Ondansetron

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Ethylamines; Benzhydryl Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Weidong Jiang, Ph.D.

  Henlix, Inc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, open-label, dose-escalation study of HLX07 ,3+3 design

Study Record Dates

• First Submitted: December 27, 2015
• First Posted: January 7, 2016
• Study Start: September 1, 2016
• Primary Completion: June 28, 2019
• Study Completion: June 28, 2019
• Last Updated: July 30, 2019

Record last verified: 2018-03

Locations

US (1); TW (1)