A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients with squamous cell carcinoma of the head and neck

TY - JOUR

T1 - A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients with squamous cell carcinoma of the head and neck

AU - Machiels, J-P

AU - Specenier, P

AU - Krauß, J

AU - Dietz, A

AU - Kaminsky, M-C

AU - Lalami, Y

AU - Henke, M

AU - Keilholz, U

AU - Knecht, R

AU - Skartved, N J

AU - Horak, I D

AU - Pamperin, P

AU - Braun, S

AU - Gauler, T C

PY - 2015/7

Y1 - 2015/7

N2 - PURPOSE: The purpose of the trial was to assess the efficacy and tolerability of Sym004, a novel 1:1 mixture of two chimeric monoclonal antibodies (992 and 1024) targeting non-overlapping epitopes of the anti-epidermal growth factor receptor (EGFR), in patients with squamous cell carcinoma of the head and neck (SCCHN).METHODS: Incurable, recurrent and/or metastatic SCCHN patients with acquired resistance to anti-EGFR monoclonal antibody-containing treatment received weekly infusions of 12 mg/kg Sym004 until disease progression or unacceptable toxicity.RESULTS: Among the 26 patients treated with Sym004, the proportion of patients alive without disease progression at 6 months was 12 % (95 % CI 1-39 %). The median duration of progression-free survival was 82 days (95 % CI 41-140 days). Of 19 patients evaluable for response, eight showed a decrease in the sum of the largest diameter in their target lesions (median 11 %; range 7-27 %). The best overall response was stable disease in 13 patients (50 %). Paired biopsies showed a significant down-regulation of EGFR in both skin and tumors following exposure to Sym004. All patients had EGFR-related adverse events, including grade 3 skin toxicities and grade ≥3 hypomagnesemia reported in 13 (50 %) and 10 (38 %) of 26 patients, respectively. One event fulfilling the protocol-defined criteria for infusion-related reactions (grade 2) was reported. No anti-drug antibodies were detected.CONCLUSIONS: The marked EGFR down-regulation shown in target tissues supports the proposed mechanism of action of Sym004. This trial revealed modest anti-tumor activity of Sym004 in extensively pretreated advanced SCCHN patients.

AB - PURPOSE: The purpose of the trial was to assess the efficacy and tolerability of Sym004, a novel 1:1 mixture of two chimeric monoclonal antibodies (992 and 1024) targeting non-overlapping epitopes of the anti-epidermal growth factor receptor (EGFR), in patients with squamous cell carcinoma of the head and neck (SCCHN).METHODS: Incurable, recurrent and/or metastatic SCCHN patients with acquired resistance to anti-EGFR monoclonal antibody-containing treatment received weekly infusions of 12 mg/kg Sym004 until disease progression or unacceptable toxicity.RESULTS: Among the 26 patients treated with Sym004, the proportion of patients alive without disease progression at 6 months was 12 % (95 % CI 1-39 %). The median duration of progression-free survival was 82 days (95 % CI 41-140 days). Of 19 patients evaluable for response, eight showed a decrease in the sum of the largest diameter in their target lesions (median 11 %; range 7-27 %). The best overall response was stable disease in 13 patients (50 %). Paired biopsies showed a significant down-regulation of EGFR in both skin and tumors following exposure to Sym004. All patients had EGFR-related adverse events, including grade 3 skin toxicities and grade ≥3 hypomagnesemia reported in 13 (50 %) and 10 (38 %) of 26 patients, respectively. One event fulfilling the protocol-defined criteria for infusion-related reactions (grade 2) was reported. No anti-drug antibodies were detected.CONCLUSIONS: The marked EGFR down-regulation shown in target tissues supports the proposed mechanism of action of Sym004. This trial revealed modest anti-tumor activity of Sym004 in extensively pretreated advanced SCCHN patients.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Monoclonal

KW - Carcinoma, Squamous Cell

KW - Cell Line, Tumor

KW - Disease Progression

KW - Disease-Free Survival

KW - Female

KW - Head and Neck Neoplasms

KW - Humans

KW - Male

KW - Middle Aged

KW - Receptor, Epidermal Growth Factor

U2 - 10.1007/s00280-015-2761-4

DO - 10.1007/s00280-015-2761-4

M3 - SCORING: Journal article

C2 - 25952795

VL - 76

SP - 13

EP - 20

JO - CANCER CHEMOTH PHARM

JF - CANCER CHEMOTH PHARM

SN - 0344-5704

IS - 1

ER -