435P - Development of PF-06439535, a potential biosimilar to bevacizumab

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Clinical research
Non-Small-Cell Lung Cancer, Metastatic
Presenter Ira Jacobs
Citation Annals of Oncology (2016) 27 (suppl_9): ix136-ix138. 10.1093/annonc/mdw593
Authors I.A. Jacobs1, P.R. Brown2, B. Knight3, M.A. Peraza4, J.A. Rosenberg5, K. Rule6
  • 1Global Medical Affairs, Pfizer Inc, 10017-5755 - New York/US
  • 2Global Supply, Pfizer Inc, Andover/US
  • 3Global Product Development, Pfizer Inc, La Jolla/US
  • 4Drug Safety R&d, Pfizer Inc, Andover/US
  • 5Global Established Pharma, Pfizer Inc, Groton/US
  • 6Global R&d, Pfizer Inc, Andover/US

Abstract

Background

PF-06439535 is being developed as a potential biosimilar to bevacizumab. Similarity of PF-06439535 to bevacizumab sourced from the EU and US (bevacizumab-EU and bevacizumab-US) was assessed using structural, functional, nonclinical toxicokinetics (TK) and toxicity, and clinical studies.

Methods

Amino acid sequences of bevacizumab-US, bevacizumab-EU and PF-06439535 were compared by peptide mapping. Functional similarity was assessed using a cell growth inhibition assay in human umbilical vein endothelial cells. PF-06439535 and bevacizumab-EU were evaluated in a 4-week, repeat-dose toxicity/TK study in male cynomolgus monkeys. In a phase 1 study, 102 healthy males received a single 5 mg/kg IV dose of PF-06439535, bevacizumab-US or bevacizumab-EU. Pharmacokinetic (PK) similarity was demonstrated for a given test-to-reference comparison if the 90% CI was within 80.00%-125.00%. Safety and immunogenicity were assessed up to 100 days post-dose.

Results

PF-06439535, bevacizumab-EU and bevacizumab-US had identical primary amino acid sequences. Similar dose responses and biological activity between PF-06439535, bevacizumab-EU and bevacizumab-US were observed in vitro. The only finding in the monkey toxicity study was the expected pharmacodynamic response of physeal dysplasia, which was similar between PF-06439535 and bevacizumab-EU. In the phase 1 study, PK was similar for PF-06439535, bevacizumab-EU and bevacizumab-US, with 90% CI of Cmax, AUCT and AUC0-∞ within 80.00%–125.00% for each pair-wise comparison. The safety profile, including anti-drug antibodies, was similar in the 3 groups with no significant safety findings.

Conclusions

To date, evaluation of PF-06439535 supports its development as a potential biosimilar to bevacizumab. An ongoing, phase 3, randomised, double-blind clinical trial is comparing the efficacy, safety, PK and immunogenicity of PF-06439535 vs bevacizumab-EU, in combination with paclitaxel and carboplatin, in previously untreated patients with advanced non-squamous non-small cell lung cancer.

Clinical trial indentification

NCT02031991 and NCT02364999.

Legal entity responsible for the study

Pfizer Inc

Funding

Pfizer Inc

Disclosure

I.A. Jacobs, P.R. Brown, B. Knight, M.A. Peraza, J.A. Rosenberg, K. Rule: Is an employee of Pfizer and owns stocks.