Date: 2014-05-29
Type of information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the 50th American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 to June 3, 2014, in Chicago
Company: Symphogen (Denmark)
Product: Sym004
Action
mechanism: Sym004 is a drug mixture of two mAbs targeting non-overlapping epitopes of EGFR which have been shown in pre-clinical studies to demonstrate synergistic inhibition of EGFR.
Disease: metastatic colorectal cancer (mCRC)
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On May 29, 2014, Symphogen, a private biopharmaceutical company with leadership in recombinant antibody mixtures for therapeutic use, reported preliminary safety and exploratory efficacy data from a Phase 1 clinical study of Sym004, an investigational anti-EGFR monoclonal antibody mixture, administered biweekly, that will be presented in a poster at the g American Society for Clinical Oncology (ASCO) Annual Meeting being held May 30 – June 3, 2014 in Chicago, IL. The poster is entitled, Phase 1 study of biweekly (Q2W) anti-EGFR monoclonal antibody (mAb) mixture Sym004 in patients (29 pts) with metastatic colorectal cancer (mCRC) resistant to previous anti-EGFR treatment (abstract #3551). The ASCO data reports on 29 patients, whose median age was 64 years. Of the 29 patients, 86% had received more than two prior lines of therapy. One cohort of 12 patients was treated at 12 mg/kg and an additional 17 patients were treated at 18 mg/kg of Sym004 Q2W.
Safety Findings: No new or unexpected toxicities were identified. Drug-related adverse effects were manageable with dose reduction and supportive medication. In the 12 and 18 mg/kg cohorts, grade 3 skin rash was seen in 4/12 [33%] and 7/17 [41%] patients, respectively (no grade 4), and grade ≥ 3 hypomagnesaemia was seen in 3/12 [25%] and 6/17 [35%] patients, respectively. Grade 3 diarrhea was seen in one patient of each cohort (8%; 6%; no grade 4). Infusion-related reactions were observed in 2/29 (7%) patients (grade 1 and 2, each).
Efficacy Findings: Antitumor activity, measured as disease control (stable disease [SD] + partial response [PR]), was documented in 14/29 (48%) patients.
* On June 2, 2013, Symphogen, a private biopharmaceutical company developing recombinant antibody mixtures, has announced at the 2013 Annual Meeting of the American Society of Clinical Oncology ( ASCO) the results of a proof-of-concept study of SYM004, an anti-EGFR monoclonal antibody (mAb) mixture. Symphogen entered the antibody mixture into the clinic in 2010, and subsequently partnered with Merck KGaA, in September 2012.
Metastatic Colorectal Cancer Phase 1 / 2 Results: Weekly doses of Sym004 showed clinical responses in mCRC patients failing previous anti-EGFR mAb treatment. Partial responses were seen at both the 12 mg/kg and 9 mg/kg doses:
• A central and blinded review of CT scans was performed in 27/29 patients treated with 12 mg/kg Sym004 and showed tumor shrinkage >10% in 7/27 (26%) pts. A partial response (PR) PR was observed in 3/27 (11%) and stable disease (SD) in 16/27 (59%).
• A central and blinded review of CT scans was performed in 12/13 patients treated with 9 mg/kg Sym004 and showed tumor shrinkage >10% in 4/12 (33%) pts. A PR was observed in 1/12 (8%) and SD in 8/12 (67%).
• PFS for 9 mg/kg and 12 mg/kg was 14 weeks (95% CI 5.3 – 22.1%) and 14.3 weeks (95% CI 6.0 – 18.6), respectively.
• The observed safety profile was similar to other anti-EGFR mAbs, except for skin related toxicity.
• EGFR down-modulation was observed in paired skin and tumor biopsies supporting the proposed mechanism-of-action.
As of 21-May-2013, 105 patients have been treated with Sym004 in clinical trials. The most frequently reported adverse events from the preliminary clinical data include, skin rash, dermatitis acneiform, erythema, nausea, fatigue hypocalcemia and hypomagnesemia. Exposure data from the patients, after weekly repeated infusions, do not indicate an anti-drug antibody response.
