Sym004 in Subjects With Stage IV Non-small Cell Lung Cancer

Phase 1

Terminated

Brief 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.

Recruitment & Eligibility

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

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Dose Limiting Toxicities (DLTs)	Day 1 to Day 21 of Cycle 1	DLT: any National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 Grade 4 hematologic or Grade 3/4 non-hematologic toxicities that occurred during DLT observation period and were considered by Investigator to be at least possibly related to trial treatment, and were confirmed by Safety Monitoring Committee (SMC), with exception of Grade 4 neutropenia for not \>5 days; Grade 4 lymphocytopenia/ thrombocytopenia for not \>5 days; fatigue/headache lasting \< 7 days; nausea/vomiting/diarrhoea lasting not \>3 days; asymptomatic Grade 3 increase in liver function tests that resolve to baseline within 7 days; Mucositis \>= Grade 3 lasting \< 7 days; Grade 3 hyperglycemia that resolves in \< 7 days; any laboratory values \>Grade 3 without any clinical correlate (resolve within 5 days); Grade 3 skin toxicities that resolve to Grade 2 within 7 days; Grade 3/4 hypomagnesemia that resolves within 5 days. Subjects with DLTs presented based on investigator and SMC decision.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death	Day 1 up to 28 days after last dose of study drug (up to 53 weeks)	An adverse event (AE) was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. AEs were considered treatment emergent if they started on or after the day of first administration of the first trial treatment given (Sym004 or one of the individual Platinum-Doublet therapies) or if they worsened after receiving first dose of treatment.

Locations (2): Please contact the Merck KGaA Communication Center located in
🇩🇪
Darmstadt, Germany
Please Contact U.S. Medical Information Located in
🇺🇸
Rockland, Massachusetts, United States