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

• ClinicalTrials.gov Identifier: NCT02083679
• Recruitment Status: Terminated
• First Posted: March 11, 2014
• Results First Posted: October 25, 2016
• Last Update Posted: October 25, 2016
• Sponsor: EMD Serono
• Information provided by (Responsible Party): EMD Serono

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Non-Small-Cell Lung	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	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: July 2014
• Actual Primary Completion Date: August 2015
• Actual Study Completion Date: August 2015

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With Dose Limiting Toxicities (DLTs) [ Time Frame: 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 :

1. Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death [ Time Frame: 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.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Massachusetts

Please Contact U.S. Medical Information Located in

Rockland, Massachusetts, United States

Germany

Please contact the Merck KGaA Communication Center located in

Darmstadt, Germany

Sponsors and Collaborators

EMD Serono

Investigators

• Study Director: Medical Responsible; Merck KGaA, Darmstadt, Germany

More Information

• Responsible Party: EMD Serono
• ClinicalTrials.gov Identifier: NCT02083679
• Other Study ID Numbers: EMR200637-003; 2013-003995-11 ( EudraCT Number )
• First Posted: March 11, 2014
• Results First Posted: October 25, 2016
• Last Update Posted: October 25, 2016
• Last Verified: August 2016

Keywords provided by EMD Serono:

Carcinoma, Non-Small-Cell Lung; Sym004

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Carboplatin; Pemetrexed; Antibodies, Monoclonal; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors