Phase 1
Phase 2
Phase 3

Dose escalation part of the Phase 1/2a trial has been completed and therapeutic dose established, and Sym0215 is now being evaluated for antitumor activity when administered at the recommended Phase 2 dose.

Overview

Sym015, a mixture of two mAbs, is a differentiated MET inhibitor for the treatment of solid tumors across several indications. MET is a member of the receptor tyrosine kinase family.

Recent results suggest that MET amplification identifies a small but clinically important subgroup of cancer patients who are likely to benefit from MET targeting. Although MET amplification occurs in a relatively small percentage of patients, it is present in various solid tumors such as lung, colorectal, RCC and
gastric carcinomas. Which indications we will pursue with Sym015 is dependent on the clinical findings in the ongoing Phase 2a expansion trial.

Target
MET
Trial
Phase 2a ongoing

Mechanism of action

The two antibodies of Sym015 bind to non-overlapping epitopes on the SEMA-a domain of MET. This allows the antibodies to bind simultaneously to the receptor and effectively induce receptor internalization and degradation. Through this mechanism, Sym015 inhibits tumor cell growth and proliferation in vitro and tumor growth in vivo, in models where MET is constitutively activated. Sym015 blocks binding of the ligand HGF to the receptor and thereby inhibits ligand-induced MET activation.

Publication

Sym015: A highly efficacious antibody mixture against MET amplified tumors

Poulsen TT, Grandal MM, Skartved NJØ, Hald R, Alifrangis L, Koefoed K, Lindsted T, Fröhlich C, Pollmann SE, Eriksen KW, Dahlman A, Jacobsen HJ, Bouquin T, Pedersen MW, Horak ID, Lantto J, Kragh M.
Clin Cancer Res. 2017 Jul 5. pii: clincanres.0782.2017. doi: 10.1158/1078-0432.CCR-17-0782. [Epub ahead of print]
PMID: 28679766 [PubMed - as supplied by publisher]

MET amplification in solid tumors

Sym015 has potential to treat patients with solid tumors showing alterations and/or amplification of the MET proto-oncogene including certain lung cancers and colorectal cancer. METexon 14 alterations for instance are detected in approximately 3–4% of lung adenocarcinomas and 20–30% of pulmonary sarcomatoid carcinomas. The prevalence of MET amplification in NSCLC ranges from 1% to 5%. In colorectal cancer the prevalence of MET amplification has been reported anywhere from 1% up to 23% depending on EGFR mutational status.

Publications

Read more about our mAb mixtures