662TiP - Pilot study of tigatuzumab (CS-1008) in combination with FOLFIRI in patients with metastatic colorectal cancer (CRC)

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Drug Development
Colon Cancer
Rectal Cancer
Presenter George Kim
Authors G. Kim1, M. Borad2, H. Pitot3, J. Rubin3, J. Greenberg4, P. McCroskery4, R. Beckman4, A. Grothey3
  • 1Gi Oncology, Mayo Clinic, 32224 - Jacksonville/US
  • 2Hematology/oncology, Mayo Clinic, Scottsdale/US
  • 3Gi Oncology, Mayo Clinic, Rochester/US
  • 4Development, Daiichi Sankyo Pharma, Edison/US

Abstract

Background

Tigatuzumab (T) is a humanized monoclonal antibody that acts as a death receptor 5 (DR5) agonist. Preclinical studies have shown that T monotherapy induces apoptosis in DR5-positive CRC cell lines and significantly inhibits growth in CRC xenograft models. T combined with FOLFIRI (folinic acid, 5-fluorouracil (5-FU), irinotecan) has demonstrated enhancement of preclinical antitumor activity. This pilot study assessed efficacy and safety of this combination therapy in patients (pts) with metastatic CRC.

Methods

This was an open-label, single-arm, multicenter study of T plus FOLFIRI in pts with histologically-confirmed metastatic CRC, an ECOG (Eastern Cooperative Oncology Group) score ≤ 2, and adequate organ and bone marrow function. Pts were non-homozygous for UGT1A1*28 allele. T was initially administered intravenously (IV) at 6 mg/kg and thereafter at 2 mg/kg weekly with one treatment cycle = 4 weeks (wks). FOLFIRI was administered IV at wks 1 and 3: irinotecan 180mg/m2, folinic acid (leucovorin) 400mg/m2 and 5-FU 400mg/m2 bolus followed by 2400 mg/m2 over 46-48 hours. Radiographic assessments were performed every 8 wks.

Results

Treated pts (n = 21) had a median of 3 prior therapies; 10 (48%) had prior FOLFIRI. All pts experienced ≥1 treatment-emergent adverse event (TEAE); the most common T-related TEAEs were fatigue (12 pts; 57%) and nausea (8 pts; 38%). 17 pts (81%) experienced a ≥ grade 3 TEAE; the most common was neutropenia (9 pts; 43%) which was partly attributed to T in 5 pts (24%). Serious AEs (SAEs) occurred in 15 pts (71%). The most common SAE was anemia (3 pts; 14%), all unrelated to T. There was 1 SAE of neutropenia related to T. Median progression-free survival (PFS) was 3.7 months. 2 pts had unconfirmed partial response; 9 pts had stable disease. The trial is ongoing.

Conclusions

T displays acceptable safety and tolerability when combined with FOLFIRI. The observed median PFS compares favorably with historical results in 3rd/4th line treated pts, but study size and single arm design preclude formal conclusions. The SAEs reported were comparable to those reported for T in combination with other chemotherapies.

Disclosure

J. Greenberg: Full-time employee of and stockholder in Daiichi Sankyo Pharmaceutical Development.

P. McCroskery: Full-time employee of and stockholder in Daiichi Sankyo Pharmaceutical Development. Stockholder in Johnson & Johnson Corporation.

R. Beckman: Full-time employee of and stockholder in Daiichi Sankyo Pharmaceutical Development. Stockholder in Johnson & Johnson Corporation.

A. Grothey: Contracted researcher for Daiichi Sankyo Pharmaceutical Development.

All other authors have declared no conflicts of interest.