The Safety,Efficacy of Anti-EGFR Humanized Monoclonal Antibody Combined With Chemotherapy in Advanced Solid Tumors.

NCT03577704 | Completed Phase 1

• 1 other identifier: HLX07-002
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

HLX07 is a new anti-EGFR monoclonal antibody (mAb) with improved glycosylation pattern.In pre-clinical efficacy studies, HLX-07 is either equivalent or more potent than cetuximab in multiple cancer models without increased toxicities.This study is an open-labeled, dose-escalation study designed to explore the maximum tolerated dose (MTD) and safety of HLX07 in combination with different chemotherapy regimens.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• The maximum tolerated dose of HLX07 combined with different chemotherapy regimen

  The incidence of DLT combined with different chemotherapy regimens based on NCI CTCAE v4.03

  up to 24 months

Study Arms (3)

HLX07+Gemcitabine+Cisplatin arm

EXPERIMENTAL

HLX07 is given on D1,D8,D15 combine with Gemcitabine (1000 mg/m2) and Cisplatin (75 mg/m2) in 3 weeks- cycles for 4-6 cycles .Gemcitabine was administered on the D1 and D8 and cisplatin 75 mg/m2 was administered on the D1. After 4-6 cycles of combination therapy, once weekly HLX07 infusion will be continue for a maximum duration of 2 years or until disease progression or emergence of intolerable toxicity or permanent withdrawal or death (whichever comes first). In each cohort, HLX07 will use BOIN design to assign the subject's dose level and determine the MTD.

Drug: HLX07+Gemcitabine+Cisplatin

HLX07+Paclitaxel+Carboplatin arm

EXPERIMENTAL

HLX07 is given on D1,D8,D15 combine with Paclitaxel (80 mg/m2) and carboplatin (AUC=2) in 3 weeks-cycle for 4-6 cycles .Paclitaxel and carboplatin were administered on D1, D8 and D15. After 4-6 cycles of combination therapy, once weekly HLX07 infusion will be continue for a maximum duration of 2 years or until disease progression or emergence of intolerable toxicity or permanent withdrawal or death (whichever comes first). In each cohort, HLX07 will use BOIN design to assign the subject's dose level and determine the MTD.

Drug: HLX07+Paclitaxel+Carboplatin

HLX07+mFOLFOX6 arm

EXPERIMENTAL

HLX07 is given on D1,D8 combine with mFOLFOX6 ( oxaliplatin (85 mg/m2), leucovorin (400 mg/m2), and 5-FU (400 mg/m2, followed by 2400 mg/m2) in 2 weeks-cycles for 6-12 cycles . Oxaliplatin, leucovorin and 5-FU were administered on D1. After 6-12 cycles of combination therapy,once weekly HLX07 infusion will be continue for a maximum duration of 2 years or until disease progression or emergence of intolerable toxicity or permanent withdrawal or death (whichever comes first). In each cohort, HLX07 will use BOIN design to assign the subject's dose level and determine the MTD.

Drug: HLX07+mFOLFOX6

Interventions

HLX07+Gemcitabine+Cisplatin DRUG

Recombinant anti-EGFR humanized monoclonal antibody in combination with Gemcitabine and Cisplatin. HLX07, IV, weekly.

Also known as: Recombinant anti-EGFR humanized monoclonal antibody, Gemzar, Cisplatin

HLX07+Gemcitabine+Cisplatin arm

HLX07+Paclitaxel+Carboplatin DRUG

Recombinant anti-EGFR humanized monoclonal antibody in combination with Paclitaxel and Carboplatin. HLX07, IV, weekly.

Also known as: Recombinant anti-EGFR humanized monoclonal antibody, Paclitaxel, Carboplatin

HLX07+Paclitaxel+Carboplatin arm

HLX07+mFOLFOX6 DRUG

Recombinant anti-EGFR humanized monoclonal antibody in combination with Oxaliplatin, Calcium Folinate and 5-FU. HLX07, IV, weekly.

Also known as: Recombinant anti-EGFR humanized monoclonal antibody, Oxaliplatin for Injection, Folinic acid calcium salt hydrate, 5-fluouracil

HLX07+mFOLFOX6 arm

Eligibility Criteria

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

You may qualify if:

• Patients with histologically confirmed metastatic or recurrent advanced solid tumors which has indication to receive treatment with one of above three chemotherapy regimens.The lesions must be assessable based on the RECIST v1.1 criteria.The number of previously received chemotherapy regimens should not exceed two.
• At least 28 days from prior major surgery, prior cytotoxic chemotherapy, or prior therapy with investigational agents or local radiotherapy and at least 42 days from the last infusion of immune check point inhibitors (The antibodies or drugs include but not limited to IDO, PD-1, PD-L1, IL-2R, CTLA-4, CD137, and GITR) before the first infusion of investigational product.
• Eastern Cooperative Oncology Group (ECOG) score ≤ 1,
• Expected survival time ≥ 3 months;
• Has sufficient hematological function, defined as: neutrophil absolute value ≥ 1.5 × 109 / L; hemoglobin level ≥ 9.0 g / dL ; Platelet count ≥100×109 /L.
• Has sufficient liver function, defined as: total bilirubin level ≤ 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN, For patients with known liver metastases or primary hepatocellular carcinoma patients ≤ 5 x ULN.
• Has adequate coagulation function defined as: International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 x ULN, and activated partial thromboplastin time (PTT) in the absence of anticoagulant therapy /aPTT) ≤ 1.5 x ULN.
• Has adequate cardiac function, defined as: left ventricular ejection fraction (LVEF) ≥ 50%.
• Has sufficient renal function; in patients receiving the gemcitabine plus cisplatin regimen is defined as creatinine clearance ≥ 60 ml/min and in patients receiving the paclitaxel plus carboplatin regimen or the mFOLFOX6 regimen, is defined as creatinine clearance ≥ 50 ml/min (calculated by the Cockcroft-Gault formula).
• Use of effective contraceptive measures if procreative potential exists.
• Able to provide written informed consent.

You may not qualify if:

• Concurrent unstable or uncontrolled medical conditions. Either of the followings:
• Active systemic infections;
• Poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg), or poor compliance with anti-hypertensive agents;
• Clinically significant arrhythmia, unstable angina pectoris, congestive heart failure (class III or IV of New York Heart Association (NYHA)) or acute myocardial infarction within 6 months;
• Uncontrolled diabetes or poor compliance with hypoglycemic agents;
• The presence of chronically unhealed wound or ulcers;
• Other chronic diseases, which, in the opinion of the investigator, could compromise safety of the patient or the integrity of study.
• Unstable central nervous system (CNS) metastasis. Patients who have previously undergone surgery or radiotherapy for brain metastases may participate in this study if they are clinically stable for at least 4 weeks and has stopped steroids for at least 2 weeks prior to the first infusion of the test drug and there is no new evidence of progression.
• Has primary central nervous system malignancy;
• Known patients have drug allergies to specific drug regimens (eg anti-EGFR monoclonal antibodies, gemcitabine, platinum, paclitaxel, fluorouracil allergy);
• known active hepatitis B or C infection (active hepatitis B is defined as hepatitis B surface antigen HBsAg positive and Hepatitis B virus (HBV) DNA\> 500 copies / ml; active hepatitis C is defined as hepatitis C antibody-positive and / or quantitative Hepatitis C virus (HCV) RNA results positive);
• Human immunodeficiency virus infection .
• Pregnancy or breast-feeding woman.
• Patients with colorectal cancer whose tumors have K-ras, N-ras, or B-raf mutations;
• The patient has a history of alcohol abuse or drug abuse;

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200123, China

Location

Related Publications (1)

• M.M. Hou, C.L. Ho, H.Y. Lin, W. Jiang, S. Liu, Y. Hong, A. Luk, S.F. Lin, T.C. Hsieh, E. Liu. A novel anti-EGFR antibody HLX07 for potential treatment of squamous cell carcinoma of the head and neck. Annals of Oncology. Volume 30 | Supplement 9 | November 2019.

  BACKGROUND

Related Links

• ESMO Asia 2019 (Poster); Annals of Oncology

MeSH Terms

Interventions

Gemcitabine; Cisplatin; Paclitaxel; Carboplatin; Oxaliplatin; Injections

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Jin E Li, PhD

  No.1800 Yuntai Road,Pudong District,Shanghai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study used the Bayes optimal interval design (BOIN) to assign the subject's dose level and determine the maximum tolerated dose (MTD) of HLX07 in combination with chemotherapy.Each cohort contains 3 subjects and the patient in the first cohort receives treatment at the lowest dose level (single dose of 400 mg). The decision to increase or decrease the dose after each train is based on the probability of a predefined safety and toxicity threshold. When the observed rate of dose limiting toxicity (DLT) is less than 0.237 (low target safety margin), the dose for the next cohort escalates; when the observed rate of DLT is higher than 0.359 (target high toxicity cutoff), the dose deescalates. Otherwise, the dose remains the same. After each cohort is finished, a safety review committee will be held to determine the escalates or deescalates in the next cohort. The enrollment continues until the maximum 30 patients are reached.

Study Record Dates

• First Submitted: June 11, 2018
• First Posted: July 5, 2018
• Study Start: August 8, 2018
• Primary Completion: September 30, 2022
• Study Completion: December 30, 2022
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

CN (1)