Randomized, Open Label, Phase III Trial of Figitumumab in Combination with Paclitaxel and Carboplatin versus Paclitaxel and Carboplatin in Patients with Non-Small Cell Lung Cancer (NSCLC) J Jassem , CL Langer, DD Karp, T Mok, S Novello, K Park, J Strausz, RJ Benner, S Green and A Gualberto Abstract 7500 Medical University, Gdansk, Poland; Abramson Cancer Center, Philadelphia, PA; MD Anderson Cancer Center, Houston, TX; Chinese University, Hong Kong, New Territories; University of Turin, Italy; Sungkyunkwan University, Seoul, Korea; Koranyi Natl. Inst. for Pulmonology, Budapest, Hungary; Pfizer Oncology, New London, CT
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Randomized, Open Label, Phase III Trial of Figitumumab in Combination with Paclitaxel and Carboplatin versus Paclitaxel and Carboplatin in Patients with.
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Randomized, Open Label, Phase III Trial
of Figitumumab in Combination with Paclitaxel and Carboplatin
versus Paclitaxel and Carboplatin in Patients
with Non-Small Cell Lung Cancer (NSCLC)J Jassem, CL Langer, DD Karp, T Mok,
S Novello, K Park, J Strausz, RJ Benner, S Green and A Gualberto
Abstract 7500
Medical University, Gdansk, Poland; Abramson Cancer Center, Philadelphia, PA;
MD Anderson Cancer Center, Houston, TX; Chinese University, Hong Kong, New Territories; University of Turin, Italy; Sungkyunkwan University, Seoul,
Korea; Koranyi Natl. Inst. for Pulmonology, Budapest, Hungary; Pfizer Oncology, New London, CT
Insulin Like Growth Factor 1 Receptor
• Central component of a signal transduction pathway that includes the IGF-1 and IGF-2 ligands and their binding proteins (IGFBPs 1 to 7)1
– IGFBPs regulate IGFs bioavailability and biological activity
• IGFs are survival factors for normal and cancer cells
– High circulating IGF-1 levels are associated with increased risk of cancer related death2
– Low circulating IGF-1 levels are associated with increased risk of heart failure and myocardial events3
1. Pollak M. Nat Rev Cancer 2008;8:915-928 2. Major JM et al. J Clin Endocrinol Metab. 2010;95:1054-9.3. Laughlin GA et al. J Clin Endocrinol Metab. 2004; 89:114-
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Figitumumab (CP-751,871)
Fully human IgG2 subtype monoclonal antibody against the IGF-1R with a T1/2 of approximately 28 days1
Well tolerated as a single agent and in combination with chemotherapy/targeted agents in early studies2
Phase I single-agent activity in Ewing’s sarcoma3
Phase II activity in first-line NSCLC in combination with paclitaxel/carboplatin4
1. Cohen et al. Clin Cancer Res 2005;11:2063-732. Gualberto A. Expert Opin Biol Ther 2010;10:575-853. Olmos et al. Lancet Oncol 2010;11:129-354. Karp et al. J Clin Oncol. 2009 27:2516-22
Study A1016: Phase III Study of Carboplatin
+ Paclitaxel +/- Figitumumab in 1st Line NSCLC
of non-adenocarcinoma histologyTrial Design Endpoints Stratification Started
• Closed to new accrual on Sept 28, 2009 due to an imbalance in deaths related to therapy by investigator: 8 (PCF) vs 0 (PC)
– SAEs in the PCF arm included asthenia, dehydration, hyperglycemia and hemoptysis
– More cardiac events (all grades) noted on PCF (15 vs 5)
• Closed permanently to new accrual on Dec 21, 2009 (N=681) after a planned interim analysis at 225 events due to a survival HR that crossed the pre-specified futility boundary
• Biomarker analysis continues to design future studies
Conclusions
• Addition of figitumumab to standard chemotherapy did not increase overall survival in advanced non-adenocarcinoma NSCLC
• Potential benefit of figitumumab may be compromised by its side effects
• Risk/benefit of figitumumab in addition to standard chemotherapy appears to be related to the levels of circulating free IGF-1
• Additional research is necessary to verify the potential of benefit in patients with high free IGF-1
Acknowledgements
• 1016 Study Investigators and Clinical Site Personnel
• 1016 Study Team and Colleagues• M Hixon, PhD (Brown University) for free IGF-1