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The Platelet-Derived Growth Factor (PDGF) Family of Ligands and Receptors, and PDGFR Signaling Pathways

Östman A, Heldin C-H. Adv Cancer Res. 2007;97:247-274; Loizos N et al. Mol Cancer Ther. 2005;4:369-379; Schmitt J, Matei D. Clin Ovarian Cancer. 2008;1:120-126;Imclone Systems, Data on File.

PDGFRa is overexpressed in multiple tumor types, including lung, with expression being associated to aggressive phenotypes and increased metastasis

PDGFR is expressed in both tumor and stromal cells

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Olaratumab (IMC-3G3) is a fully human IgG1 monoclonal antibody targeted against platelet-derived growth factor receptor-α (PDGFRα)

Loizos N et al. Mol Cancer Ther. 2005;4:369-379; ImClone Systems. Data on file; Matei D et al. Oncogene 2006;25:2060-2069; Youssoufian H et al. J Clin Oncol. 2008;26:15s. Abstract 14617; Östman A, Heldin C-H. Adv Cancer Res. 2007;97:247-274; Schmitt J, Matei D. Clin Ovarian Cancer. 2008;1:120-126.

In preclinical studies:

Binds to PDGFRα with high affinity; Kd=40 pM Blocks receptor activation in tumor and stromal cells Inhibits activation of downstream effector molecules May cause anticancer activity by

directly inhibiting tumor growthinhibiting angiogenesis and the

surrounding tumor milieu

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Studies of olaratumab in NSCLCOngoing trials

Study ID Ph Eligibility/Line Arm(s) N (projected)

NCT00918203 II Stage IIIB/IV, first line Paclitaxel + Carboplatin IMC-3G3 + Paclitaxel +

Carboplatin136

www.clinicaltrials.gov (accessed on August 28th, 2010)

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A Randomized Phase 2 Study of IMC-3G3 With or Without Carboplatin and Paclitaxel in Patients With Previously Untreated Locally Advanced or Metastatic NSCLC

• NSCLC stage IIIB or IV

• No prior chemotherapy

or targeted therapy in

the metastatic setting

• Squamous histology

eligible

• CNS metastases

allowed

• Age ≥18

• ECOG performance

status ≤1

RANDOMIZE

IMC-3G3

IMC-3G3 15 mg/kg day 1, 8

+Taxol 200 mg/m2 day 1

+Carboplatin AUC=6 day 1

every 3 weeks x 6

Paclitaxel 200 mg/m2 day 1

+Carboplatin AUC=6 day 1

every 3 weeks x 6

N=136Primary Objective: PFS

www.clinicaltrials.gov; NCT00918203 (accessed on August 28th, 2010)4

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