{Reference Type}: Clinical Trial
{Title}: First-in-human trial exploring safety, antitumor activity, and pharmacokinetics of Sym013, a recombinant pan-HER antibody mixture, in advanced epithelial malignancies.
{Author}: Berlin J;Tolcher AW;Ding C;Whisenant JG;Horak ID;Wood DL;Nadler PI;Hansen UH;Lantto J;Skartved NJØ;Pedersen MW;Patnaik A;
{Journal}: Invest New Drugs
{Volume}: 40
{Issue}: 3
{Year}: 06 2022
{Factor}: 3.651
{DOI}: 10.1007/s10637-022-01217-7
{Abstract}: Sym013 contains six humanized monoclonal antibodies that bind to non-overlapping epitopes on three human epidermal growth factor receptors (HER1-3). Preclinical studies suggested Sym013 strongly suppresses growth of multiple epithelial tumors. This is a first-in-human study exploring safety and efficacy of Sym013 in patients with advanced epithelial malignancies.<BR>Dose escalation used single-patient cohorts until the stopping rule was met, followed by 3 + 3 design. Dose levels planned were: 1, 2, 4, 6, 9, 12, 15, and 18 mg/kg. Treatment cycles were 28 days with imaging every eight weeks. Serum samples were collected at multiple time points for assessment of pharmacokinetics and development of anti-drug antibodies.<BR>Thirty-two patients were enrolled with multiple solid tumors, most common being colorectal cancer (CRC; 10/32, 31%). Due to mucositis, rash, and diarrhea at 4 mg/kg once-weekly, dosing was changed to biweekly (Q2W). Mandatory prophylaxis was added due to Grade 3 infusion-related reaction and oral mucositis at 9 mg/kg Q2W. The 15 mg/kg Q2W cohort was enrolling when the study was terminated for business reasons. Most common adverse events were skin (81%) and gastrointestinal (75%) disorders, including dermatitis/rash, stomatitis, and diarrhea. One patient with CRC achieved a partial response; 12 patients with varied malignancies had stable disease.<BR>During the conduct of the study, management of frequent infusion-related reactions, skin toxicities, and mucosal disorders, which are indicative of HER inhibition, necessitated multiple protocol amendments. The investigators, in concert with the Sponsor, agreed that achieving a tolerated regimen with acceptable target saturation was unlikely.<BR>www.<BR>gov ; NCT02906670 (September 20, 2016).