Sym004 in SCCHN Patients Failing Anti-EGFR Based Therapy

Symphogen A/S26 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Carcinoma, Squamous Cell of Head and Neck

Interventions

Sym004DRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically confirmed diagnosis initially or at relapse of SCCHN of the oral cavity, oropharynx, hypopharynx or larynx * Recurrent and/or metastatic SCCHN not amenable to curative treatment with surgery and/or (chemo)radiation * Previous treatment with an anti-EGFR monoclonal antibody (mAb) in the palliative setting either as monotherapy or in combination with chemotherapy or radiotherapy and showing: * Documented clinical benefit or response for at least 8 weeks (PR, CR or SD) on the anti-EGFR mAb-based therapy and * Documented disease progression (verified by computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\] according to RECIST (1.1) during or within 12 weeks following the last administration of anti-EGFR mAb * Accessible tumor for biopsy and subject acceptance of repeat tumor biopsies * Other protocol-defined inclusion criteria could apply Exclusion Criteria: * More than 2 lines of prior chemotherapy in the palliative setting * Expected survival \<12 weeks * Subjects with known brain metastases * Chemotherapy or radiation therapy within 21 days prior to Visit 2 at the exception of palliative radiotherapy for bleeding or pain, which is allowed anytime, if not given on target lesions * Anti-EGFR mAbs within 14 days prior to Visit 2 * Major surgery within 4 weeks prior to Visit 2 and subjects must have recovered from effects of major surgery * Other protocol-defined exclusion criteria could apply

Locations (10)

3203; Antwerp University Hospital; Department of Medical Oncology

Antwerp, Edegem, Belgium

3202; Jules Bordet Institute; Clinique d'Oncologie Médicale

Brussels, Belgium

3201; Cliniques Universitaires St-Luc; Centre du Cancer

Brussels, Belgium

Outcomes

Primary Outcomes

Progression Free Survival (PFS) Time

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.

Time frame: Time from the first infusion of Sym004 until progressive disease or death, assessed up to 24 weeks

Secondary Outcomes

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

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.

Time frame: Time from first infusion of Sym004 until disease progression or death, assessed up to 18 months

Duration of Overall Response

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.

Data from ClinicalTrials.gov

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3303; Centre Alexis Vautrin; Département d'Oncologie Médicale

Nancy, Vandoeuvre Les Nancy, France

4905; Charité Campus Benjamin Franklin; Hematology, Oncology and Transfusion Medicine

Berlin, Germany

4901; Universitätsklinikum Essen

Essen, Germany

4904; Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

4906; University Medical Center Hamburg Eppendorf; Department of Otorhinolaryngology and Head and Neck Surgery

Hamburg, Germany

4907; University Hospital Heidelberg; Nationales Centrum für Tumorerkrankungen (NCT)

Heidelberg, Germany

4902; University of Leipzig

Leipzig, Germany

Time frame: Time from first infusion of Sym004 until disease progression or death, assessed up to 18 months

Time to Progression (TTP)

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.

Time frame: Time from first infusion of Sym04 until disease progression, assessed up to 18 months

Overall Survival Time

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.

Time frame: Time from first infusion of Sym004 until death, assessed up to 18 months

Number of Subjects With Detectable Biomarkers at Any Visit

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.

Time frame: Weeks 0 and 4; and 4 weeks after last dose

Area Under the Serum Concentration Curve From Time Zero to 168 Hours (AUC [0-168])

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