A Phase 2 Multicenter Study Evaluating the Efficacy and Safety of IMC-11F8, a Recombinant Human IgG 1 Anti-Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody (MAb), Combined With 5-FU/FA and Oxaliplatin (mFOLFOX-6) as First-Line Therapy in Patients With Advanced Colorectal Cancer (CRC).
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A Phase 2 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 in Patients With Advanced Colorectal Cancer (CRC)
Tabernero J1, Sastre Valera J2, Delaunoit T3, Cervantes A4, Hendlisz A5, Fox F6, Youssoufian H6, Rowinsky E6
1Vall d'Hebron University Hospital, Barcelona, Spain
2Hospital Universitario San Carlos, Madrid, Spain
3Centre Hospitalier Jolimont-Lobbes, Haine Saint-Paul, Belgium
4Hospital Clinico Universitario de Valencia, Valencia, Spain
5Institut Jules Bordet, Brussels, Belgium
6ImClone Systems Incorporated, Branchburg, NJ
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 cancer (CRC). 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 drug-resistant CRC xenografts. In Phase 1, IMC-11F8 has been well-tolerated with promising antitumor activity, dose-dependent elimination and nonlinear exposure consistent with saturable clearance mechanism(s). The primary endpoint of this Phase 2 study is to determine the overall response rate (ORR) to IMC-11F8 in combination with mFOLFOX-6 in patients 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 [FA] 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. Patients undergo radiologic tumor response evaluation every 8 weeks.
Results: A total of 38 patients have been enrolled and 35 patients have been treated, with 29 ongoing. Of 23 patients who have had at least one response assessment to date, 15 (65.2%) experienced partial responses (PRs) and eight patients have had a best overall response of stable disease to date. The most common adverse events (AE) were skin rash and asthenia (seven patients each). 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 patient died due to an intestinal obstruction that was not considered related to IMC-11F8 (this patient had a PR at the time of death).
Conclusions: These preliminary results suggest that the addition of IMC-11F8 to the mFOLFOX-6 regimen in metastatic CRC patients is well tolerated with notable antitumor activity. This convenient every-2-week schedule merits further evaluation in this setting.
Key Inclusion Criteria
Key Inclusion Criteria
Open label, multicenter Phase 2 trial. Treatment cycles defined as 2 weeks. Patients receive IMC-11F8 and mFOLFOX-6 chemotherapy once per treatment cycle (beginning on Day 1 of each cycle).
Radiological evaluation of response to treatment occurs once every four cycles (ie, every 8 weeks).
A total of 38 patients have been enrolled to date; 35 patients have received treatment. Twenty-nine patients continue on study. Two have discontinued due to an adverse event, including one death, and four due to withdrawal of consent or for other reasons.
Extent of Exposure
Most Common IMC-11F8 Related* Adverse Events (> 1 Patient)
* – Possibly, Probably, or Definitely Related to IMC-11F8
Summary of Best Overall Response
* – 14 of 23 patients have received only one assessment to date. Of these, 10 continue to receive treatment.