A phase II multicenter study evaluating the efficacy and safety of IMC-11F8, a recombinant human IgG1 anti- epidermal growth factor receptor (EGFR) monoclonal antibody (Mab), combined with 5-FU/FA and oxaliplatin (mFOLFOX-6) as first- line therapy

Abstract

4066 Background: Targeting the EGFR using cetuximab, a chimeric IgG1 anti-EGFR MAb, has resulted in significant clinical activity in a wide range of cancers, including colorectal neoplasms. IMC-11F8 is a recombinant human IgG1 Mab with EGFR-binding characteristics similar to those of cetuximab. In preclinical studies, IMC-11F8 has demonstrated activity alone and in combination with irinotecan and oxaliplatin in both drug-sensitive and -resistant CRC xenografts. In phase I, IMC-11F8 has been well-tolerated with promising antitumor activity, dose-dependent elimination and nonlinear exposure consistent with saturable clearance mechanism(s). This phase II study evaluated the overall response rate associated with IMC-11F8 in combination with mFOLFOX-6 in patients (pts) with unresectable, locally- advanced or metastatic CRC who have not received chemotherapy in the advanced setting. Methods: IMC-11F8 is administered at an absolute dose of 800 mg on Day 1 of each cycle followed by treatment with mFOLFOX-6 (oxaliplatin 85 mg/m², folinic acid 400 mg/m², and 5-fluorouracil [400 mg/m² bolus followed by 2400 mg/m² as a continuous 46-hour infusion]). Each cycle is repeated every 2 weeks until disease progression or toxicity requiring discontinuation. Pts undergo radiologic tumor response evaluation every 8 weeks. Results: 19 pts have been enrolled (18 ongoing). Of 10 pts who have had response assessments, six (60%) experienced partial responses (PRs). The most common adverse event (AE), at least possibly-related to IMC-11F8, was skin rash. One pt experienced a grade 2 infusion reaction to IMC-11F8 during Cycle 2. Other Aes reported to date are consistent with mFOLFOX-6 therapy. One pt died due to an intestinal obstruction that was not considered related to IMC-11F8 (this pt had a PR at the time of death). PK results will be reported. Conclusions: These preliminary results suggest that the addition of IMC-11F8 to the mFOLFOX-6 regimen in metastatic CRC pts is well tolerated with notable antitumor activity. This convenient every-2-week schedule merits further evaluation in this setting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration ImClone Systems Incorporated ImClone Systems Incorporated