The Safety,Efficacy of Anti-EGFR Humanized Monoclonal Antibody Combined With Chemotherapy in Advanced Solid Tumors.
Condition: Advanced Solid Tumors
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Detailed description: 
      This study is a parallel 3-arm escalation trial with 3 doses of HLX07 (400 mg, 600 mg, or 800
      mg per single dose) combined with 3 different fixed-dose chemotherapy regimens.

      Three chemotherapy regimens are：

      ① Gemcitabine (1000 mg/m2) and Cisplatin (75 mg/m2) , every three weeks. Gemcitabine was
      administered on the first day and on the 8th day, and cisplatin 75 mg/m2 was administered on
      the first day , a total of 4-6 cycles。

      ② Paclitaxel (80 mg/m2) and carboplatin (AUC=2), every 3 weeks. Paclitaxel and carboplatin
      were administered on days 1, 8 and 15 for a total of 4-6 cycles.

      ③ mFOLFOX6 protocol: oxaliplatin (85 mg/m2), leucovorin (400 mg/m2), and 5-fluouracil (5-FU)
      (400 mg/m2, followed by 2400 mg/m2), every 2 weeks. Oxaliplatin, leucovorin and 5-FU were
      administered on the first day.

      After 4 to 6 cycles of (gemcitabine and cisplatin regimens) and (the paclitaxel and
      carboplatin regimens) or after 6 to 12 cycles of the mFOLFOX6 regimen, well-controlled
      patients will be continue to receive a weekly HLX07 infusion as maintenance therapy for
      maximum 2 years or until disease progression or emergence of intolerable toxicity or
      permanent withdrawal or death (whichever comes first).

      The study used the Bayes optimal interval design (BOIN) to determine the MTD of HLX07 in
      combination with chemotherapy.
    

Intervention name(s): HLX07+Gemcitabine+Cisplatin; HLX07+Paclitaxel+Carboplatin; HLX07+mFOLFOX6
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Recombinant anti-EGFR humanized monoclonal antibody in combination with Gemcitabine and Cisplatin.
HLX07, IV, weekly.; Recombinant anti-EGFR humanized monoclonal antibody in combination with Paclitaxel and Carboplatin.
HLX07, IV, weekly.; Recombinant anti-EGFR humanized monoclonal antibody in combination with Oxaliplatin, Calcium Folinate and 5-FU.
HLX07, IV, weekly.
Other intervention name(s): Recombinant anti-EGFR humanized monoclonal antibody; Gemzar; Cisplatin; Recombinant anti-EGFR humanized monoclonal antibody; Paclitaxel; Carboplatin; Recombinant anti-EGFR humanized monoclonal antibody; Oxaliplatin for Injection; Folinic acid calcium salt hydrate; 5-fluouracil
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Carboplatin; Gemcitabine; Oxaliplatin; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: 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.
Masking: None (Open Label)
Primary purpose: Treatment