Symphogen announced today preliminary primary endpoint data on 12 of 20 patients enrolled in the first Phase 1 clinical trial with their lead cancer compound, Sym004. Based on the data, the poster authors concluded that Sym004 is well tolerated, and shows preliminary signs of clinical effect. A dose of 12 mg/kg Sym004 has been chosen for an on-going follow up study where the safety, efficacy and PK of Sym004 will be validated in a homogenous patient population with advanced metastatic colorectal cancer (mCRC) and wild type KRAS.
Preliminary results from the first-in-human, multicenter, Phase 1, dose-escalation trial evaluating safety and tolerability of multiple doses of Sym004 were presented at the 2011 Annual Meeting of the American Society of Clinical Oncology on June 6 by Dr. Rodrigo Dienstmann of the Vall d'Hebron University Hospital, Barcelona, Spain in a poster entitled "Phase I Trial Of The First-In-Class EGFR mAb Mixture, Sym004, In Patients With Refractory Advanced Solid Tumors." The collaborating trial centers were the START Center- South Texas Accelerated Research Therapeutics, San Antonio TX and the Vall d'Hebron University Hospital, Barcelona, Spain.
Of the 20 included patients, 13 had previously progressed on other anti-EGFR therapy. At the time of data cut-off, 12 out of 20 patients had received more than 7 weekly infusions of Sym004 (52, 32, 24, 22, 22, 13, 11, 11, 10, 8, 8, 7 weeks on treatment), based on the investigator's evaluation that patients presented with stable disease and had manageable adverse events. Only the expected adverse event profile of EGFR target mAb therapeutics was observed, i.e. diarrhea, rash, mucosal inflammation, nausea, infusion related reaction and hypomagnesemia.
The on-going PK analysis indicates that Sym004 has a concentration-dependent decrease in clearance, suggesting a two-compartment model. Peak and through serum levels of Sym004 after multiple infusions suggest that there is an accumulation of Sym004 from the 1st to 4th infusion at dose levels ≥ 6 mg/kg. Preliminary t½ of Sym004 at 12 mg/kg is ~5 days. Exposure data after weekly repeated infusions do not indicate an anti-drug antibody response.
A total of 20 patients with refractory or recurrent advanced late stage solid tumors without available therapeutic options (12 colon, 2 rectal, 2 lung, 3 pancreatic, 1 spinal chordoma), received weekly doses of Sym004. The main eligibility criteria were ECOG performance status ≤2; no evidence of brain metastases; no diarrhea or skin rash CTCAE > 1; adequate bone marrow, liver, and renal function and life expectancy of at least 3 months.
The primary endpoint of the study was adverse events. Secondary endpoints included pharmacokinetic profile; overall response rate (ORR) by RECIST; progression free survival (PFS); overall survival (OS); and host immune response.