Poster Presentation COSA-IPOS Joint Scientific Meeting 2012

A randomized, phase Ib/II trial of rilotumumab (AMG 102; ril) or ganitumab (AMG 479; gan) with panitumumab (pmab) vs pmab alone in patients with wild-type (WT) KRAS metastatic colorectal cancer (mCRC): primary and biomarker analyses (#735)

Niall C Tebbutt 1 , Eric Van Cutsem 2 , Cathy Eng 3 , Elzbieta Nowara 4 , Anna Świeboda-Sadle 5 , Edith Mitchell 6 , Irina Davidenko 7 , Kelly S Oliner 8 , Lisa Chen 8 , Jing Huang 9 , Elwyn Loh 9 , Eduard Gasal 10 , Josep Tabernero 11
  1. Austin Hospital, Heidelberg, VIC, Australia
  2. University Hospital Gasthuisberg, Leuven, Belgium
  3. The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
  4. Instytut im. M. Sklodowskiej-Curie, Gliwice, Poland
  5. Warszawski Uniwersytet Medyczny, Warszawa, Poland
  6. Thomas Jefferson University, Philadelphia, PA, USA
  7. Krasnodar City Oncology Center, Krasnodar, Russia
  8. Amgen Inc., Thousand Oaks, CA, USA
  9. Amgen Inc., South San Francisco, CA, USA
  10. Amgen (Europe) GmbH, Zug, Switzerland
  11. Vall d'Hebron University Hospital, Barcelona, Spain

Aim: Pmab, ril, and gan are fully human monoclonal antibodies against epidermal growth factor receptor, hepatocyte growth factor, and insulin-like growth factor receptor 1, respectively. The safety and efficacy of ril or gan with pmab in patients with WT KRAS mCRC is presented.

Methods: Part 2 of this 3-part study was a phase II, randomized, double-blinded, placebo-controlled trial of 3 arms: pmab (6 mg/kg)/placebo (Arm 1), pmab/ril (6/10 mg/kg, Arm 2, and pmab/gan (6/12 mg/kg, Arm 3). Administration was Q2W until disease progression or intolerance. Patients were ≥18 yrs old, had ECOG PS 0/1, and had prior irinotecan and/or oxaliplatin. The primary endpoint was objective response rate (ORR). The primary analysis of ORR used a Bayesian method. Secondary endpoints included progression-free survival (PFS) and safety. Biomarker analyses including c-Met expression by immunohistochemistry on archival tumor samples were completed.

Results: Of the 142 patients enrolled, 58% were men, mean age was 59.7 yrs, and ECOG PS of 0/1 was 40%/59%, respectively. The ORRs were 21%, 31%, and 22% and the median PFS (95% CI) were 3.7 (2.5-5.3), 5.2 (3.6-5.4), and 5.3 (2.7-5.7) months for Arms 1, 2, and 3, respectively. The posterior probability of OR >1 relative to Arm 1 for ORR were 0.93 for pmab/ril and 0.63 for pmab/gan. The most common adverse event of grade ≥ 3 in the pmab/ril arm was rash, and in the pmab/gan arm was hypomagnesemia. Immunohistochemistry results were obtained for 94% of the patients (134/142).

Conclusions: Pmab/ril met the prespecified criterion for improvement in ORR (greater than Arm 1). Pmab/gan was indeterminate. Pmab in combination with ril or gan was well tolerated. There were no strong correlations demonstrated between the expression of tumor c-MET protein and clinical outcomes. (© 2012 Amgen Inc.)