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

A Phase Ib, Open-label, Dose Escalation Trial Investigating Different Doses and Schedules of Sym004 in Combination With Platinum-doublets in Subjects With Stage IV Non-small Cell Lung Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine; Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed; Drug: Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel; Drug: Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Darmstadt, Germany
    • Please contact the Merck KGaA Communication Center located in
• United States
  • Massachusetts
    • Rockland, Massachusetts, United States
      • Please Contact U.S. Medical Information Located in

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine	Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine; 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).
Experimental: Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed	Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed; 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).
Experimental: Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel	Drug: Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel; 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).
Experimental: Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel	Drug: Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Dose Limiting Toxicities (DLTs)	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.	Day 1 to Day 21 of Cycle 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death	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.	Day 1 up to 28 days after last dose of study drug (up to 53 weeks)

Collaborators and Investigators

• Sponsor: EMD Serono

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: March 7, 2014
• First Submitted That Met QC Criteria: March 7, 2014
• First Posted (Estimate): March 11, 2014

Study Record Updates

• Last Update Posted (Estimate): October 25, 2016
• Last Update Submitted That Met QC Criteria: August 29, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Carcinoma, Non-Small-Cell Lung; Sym004
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Folic Acid Antagonists; Gemcitabine; Carboplatin; Paclitaxel; Cisplatin; Albumin-Bound Paclitaxel; Antibodies, Monoclonal; Pemetrexed
• Other Study ID Numbers: EMR200637-003; 2013-003995-11 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No