Symptoms and General Pathology

All Conditions

Neoplasms

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Sym004 will be administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.

Sym004

Ivan Horak, MD, FACP

The trial is designed as a multi-center, open label Phase 2 trial that investigates the efficacy and safety of Sym004 in subjects with squamous cell cancer of the head and neck (SCCHN). Subjects included must have responded to previous anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody-based therapy and subsequently become resistant to that therapy. It is believed that Sym004 has the potential to induce tumor responses and provide a superior treatment option to subjects with advanced SCCHN.

Symphogen was the sponsor for planning/conducting and reporting results for this trial.

Sym004 in SCCHN Patients Failing Anti-EGFR Based Therapy

An Open-label, Single Arm, Phase II Trial to Investigate the Safety and Efficacy of Sym004 in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) Who Have Failed Anti-EGFR Monoclonal Antibody-based Therapy

The PFS time was defined as the time from first infusion of Sym004 until progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. or death. PD was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The unequivocal progression of existing non-target lesions and the appearance of one or more lesions was also considered progression. Subjects who died without confirmed PD were considered as progressed. Subjects who died or showed PD more than 21 days after last treatment were censored (that is, were considered alive without progression on Day 21 after last treatment). Evaluation was done using Kaplan-Meier estimates.

Best objective tumor response was defined as the occurrence of complete response (CR), partial response (PR), stable disease (SD), or PD according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Objective response was defined as the occurrence of CR or PR according to RECIST Version 1.1. Disease control was defined as the occurrence of CR, PR or SD according to RECIST Version 1.1.

CR: Disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 mm; PR: At least a 30% decrease in the sum of diameters of all - lesions, taking as reference the baseline sum diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on trial.

Duration of overall response was defined as the time from the first time point where measurement criteria are met for CR or PR until first date of recurrence or PD was objectively documented according to RECIST Version 1.1. Duration of overall response was censored at date of last imaging data of measured lesions if no confirmation of recurrence or PD was available.

The TTP was defined as the time from first infusion of Sym004 until disease progression according to RECIST Version 1.1 criteria. Disease progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The subjects who died without prior assessment of PD were censored for TTP.

Overall survival time was defined as the time from first infusion of Sym004 until date of death. Subjects who withdraw the consent or lost to follow-up were censored.

The biomarkers human papilloma virus (HPV), mutated epidermal growth factor receptor (EGFRvIII), c-MET and human epidermal growth factor receptor (HER) 2, HER3 were analyzed only in tumor cells while EGFR, phosphorylated epidermal growth factor receptor (pEGFR), and Ki-67 were analyzed both in tumor and skin biopsy cells.

The AUC (0-168h) was estimated by determining the total area under the curve of the concentration versus time curve.

The AUC (0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

The apparent terminal half-life was defined as the time required for the serum concentration of Sym004 to decrease 50% in the final stage of its elimination.

Volume of distribution was defined as the theoretical volume in which the total amount of drug needed to be uniformly distributed to produce the desired serum concentration of a drug.

An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. 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.

Symphogen A/S

Sym004 was administered at the dose of 12 milligram per kilogram (mg/kg) as an intravenous infusion every week up to disease progression or withdrawal from treatment.

Age, Continuous

Sex: Female, Male

Full analysis set (FAS) comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.

Chief Scientific Officer

The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment.

Progression Free Survival (PFS) Time

Objective Tumor Response and Derived Endpoints (Objective Response Rate and Disease Control Rate)

Duration of overall response could not be calculated as no subject showed CR or PR.

Duration of Overall Response

Time to Progression (TTP)

Overall Survival Time

Tumor biopsy: HPV (n=19)

Tumor biopsy: EGFRvIII (n=21)

Tumor biopsy: cMET (n=19)

Tumor biopsy: HER2 (n=17)

Tumor biopsy: HER3 (n=17)

Skin biopsy: EGFR (n=18)

Tumor biopsy: EGFR (n=11)

Tumor biopsy: pEGFR (n=26)

Skin biopsy: pEGFR (n=26)

Skin biopsy: Increase in Ki67 (n=18)

Skin biopsy: Decrease in Ki67 (n=18)

Tumor biopsy: Decrease in Ki67 (n=11)

The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. "n" signifies subjects evaluable for specified biomarker type.

Number of Subjects With Detectable Biomarkers at Any Visit

Week 0 (n=26)

Week 3 (n=23)

The FAS comprised all subjects who had been exposed to trial drug irrespective of their compliance to the planned course of treatment. 'n' signifies subjects who were evaluable at given time points.

Spots Global Cancer Trial Database for Sym004 in SCCHN Patients Failing Anti-EGFR Based Therapy

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial