Sym004 in Subjects With Stage IV Non-small Cell Lung Cancer
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine; Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed; Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel; Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel
Intervention description: Sym004 will be administered as an intravenous infusion at a dose of 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject meets any of the criteria for subject withdrawal, or withdrawal from the investigational medicinal product (IMP) in combination with platinum-doublet chemotherapy regimen of cisplatin/gemcitabine (cisplatin 75 mg/m^2 on Day 1 plus gemcitabine 1250 mg/m^2 on Days 1 and 8 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).; Sym004 will be administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject meets any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of cisplatin/pemetrexed (cisplatin 75 mg/m^2 plus pemetrexed 500 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).; Sym004 will be administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject meets any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin area under the concentration-time curve (AUC) = 6 milligram per millilitre per minute [mg/mL/min] plus paclitaxel 225 mg/m^2 on Day 1 of 3-Week cycle intravenously for a maximum of 6 treatment cycles).; Sym004 will be administered as an intravenous infusion at a dose 6 mg/kg on Day 1 and 12 mg/kg on Day 8 of a 3-Week cycle until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject meets any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin AUC = 6 mg/mL/min plus paclitaxel 225 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Carboplatin; Gemcitabine; Pemetrexed; Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Carcinoma, Non-Small-Cell Lung; Sym004

Summary:

      This is a multi-center, open-label, Phase 1b, dose escalation trial of Sym004 administered in
      combination with 1 of 3 platinum-doublets in subjects with Stage IV Non-Small Cell Lung
      Cancer (NSCLC).

      The sponsor decided to discontinue the development of Sym004. Also the decision was made to
      discontinue the development of Sym004 in NSCLC indication. The decision to discontinue Sym004
      in NSCLC was not related to any safety or efficacy findings regarding Sym004. As a result of
      the early discontinuation of the trial during the dose escalation part, the expansion cohort
      will no longer be performed hence the pre-specified secondary endpoints are not analyzed and
      were removed from the protocol based on protocol amendment 2 dated 31 March 2015.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female outpatients (except where inpatient stay is required for medical need
             at the Investigator's discretion) at least 18 years of age at the time of informed
             consent

          -  Histologically-confirmed NSCLC Stage IV disease (according to the seventh edition of
             the lung cancer staging system)

          -  Eligibility for platinum-based chemotherapy

          -  Tumor tissue available for epidermal growth factor receptor (EGFR) expression analysis

          -  Measurable disease defined as 1 or more target lesions according to Response
             Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)

          -  Life expectancy of at least 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1

          -  Other protocol defined inclusion criteria could apply

        Exclusion Criteria:

          -  Previous therapy for Stage IV NSCLC, or neo- or adjuvant chemotherapy or
             chemoradiotherapy within the previous 6 months

          -  Previous investigational drug or any anticancer therapy in the 30 days (or 5
             half-lives for non-cytotoxics, whichever is shorter) prior to the start of trial
             treatment

          -  In countries where anaplastic lymphoma kinase (ALK) inhibitors are available for the
             treatment of NSCLC, subjects need to have been screened for ALK fusion gene
             rearrangements and excluded if positive, unless previously treated and progressed on
             an appropriate tyrosine kinase inhibitor (TKI) therapy

          -  In countries where EGFR TKIs are available for the treatment of NSCLC, subjects need
             to have been screened for EGFR mutations and excluded if positive, unless previously
             treated and progressed on an appropriate TKI therapy

          -  Concurrent chronic immunosuppressive or hormone anticancer therapy (except other
             physiologic hormone replacement)

          -  Known brain metastases (unless asymptomatic and treated) or leptomeningeal metastases,
             including suspected leptomeningeal spread with positive cytology

          -  History of any other malignancy within 5 years (except basal cell carcinoma of the
             skin or carcinoma in situ of the cervix)

          -  Other protocol defined exclusion criteria could apply