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

NCT02083679 | Terminated Phase 1 Results DMC

• 2 other identifiers: EMR200637-0032013-003995-11
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 2

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Carcinoma, Non-Small-Cell Lung; Sym004

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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)

Study Arms (4)

Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine

EXPERIMENTAL

Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine

Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed

EXPERIMENTAL

Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed

Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel

EXPERIMENTAL

Drug: Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel

Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel

EXPERIMENTAL

Drug: Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel

Interventions

Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine DRUG

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).

Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine

Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed DRUG

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).

Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed

Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel DRUG

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).

Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel

Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel DRUG

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).

Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• EMD Serono: lead

Study Sites (2)

Please Contact U.S. Medical Information Located in

Rockland, Massachusetts, United States

Location

Please contact the Merck KGaA Communication Center located in

Darmstadt, Germany

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cisplatin; Gemcitabine; Pemetrexed; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Limitations and Caveats

The trial was prematurely discontinued and Expansion Cohort (Part 2) was not conducted as Sponsor decided to prematurely discontinue the development of Sym004. This decision was not related to any safety or efficacy findings regarding Sym004.

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2014
• First Posted: March 11, 2014
• Study Start: July 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: October 25, 2016
• Results First Posted: October 25, 2016

Record last verified: 2016-08

Locations

US (1); DE (1)