eFFECTOR Therapeutics, Pfizer and Merck KGaA are conducting a Phase II study with the antibody and a new small molecule MNK1/2 inhibitor. 

A new Phase II study is being initiated to investigate the safety, tolerability, and efficacy of a combination treatment (CRC).

The two drugs in the therapy include eFFECTOR Therapeutics’ small-molecule investigational MAP kinase-interacting kinase 1 and 2 (MNK1/2) inhibitor eFT508 and Merck KGaA’s and Pfizer’s programmed death-ligand 1 (PD-L1) antibody avelumab (Bavencio^®). The noncomparative study is expected to be initiated during the third quarter of 2017 and will be conducted by eFFECTOR and funded by Pfizer and Merck KGaA.

The eFFECTOR technology is based on research conducted at the University of California, San Francisco (UCSF). The company was founded in 2012 to develop a new class of cancer-targeting selective translation regulators (STRs) based on the technology. In addition to eFT508, eFT226 is in preclinical studies. This compound is a selective small-molecule inhibitor of eurkaryotic initiation factor 4A (eIF4A), which the company says is a difficult target that is associated with diseases that have poor prognoses. eFFECTOR expects to file an IND application for eFT226 with the FDA by the end of 2017. The company is also developing a number of other small-molecule inhibitors of eIF4E.

The small-molecule MNK1/2 inhibitor is an orally administered, highly potent drug that inhibits MNK1 and MNK2, which are terminal kinases in key oncogenic signaling pathways. It was designated an orphan drug by the US FDA in March 2017 for the treatment of diffuse large B-cell lymphoma. It is already being investigated in other clinical trials (Phase I/II) for the treatment of patients with solid tumors and lymphoma. According to eFFECTOR, preclinical data suggests that eFT508 on its own induces antitumor immunity and immune memory, but also acts synergistically with checkpoint inhibitors.

"We believe eFT508, our lead program, is a promising new immuno-oncology drug candidate that could significantly improve patient response in combination with checkpoint inhibitors," said Steve Worland, Ph.D., President and CEO at eFFECTOR.

The partnership between Pfizer and Merck KGaA to develop and commercialize avelumab was established in 2014. The drug received accelerated approval for the treatment of metastatic Merkel cell carcinoma from FDA in March 2017 and approval for the treatment of U.S. regulator approved avelumab for treating locally advanced or metastatic urothelial cell carcinoma in May 2017. The antibody is also being investigated for the treatment of numerous different tumors in the JAVELIN clinical trial program, which involves nine or more Phase III clinical trials.

Noted Alise Reicin, M.D., Head of Global Clinical Development at Merck KGaA: "We look forward to exploring the potential of this novel combination and the role we hope it may eventually have for improving the treatment of CRC.” Chris Boshoff, M.D., Ph.D., SVP and Head of Immuno-oncology, Early Development, and Translational Oncology, Pfizer Global Product Development, added that "eFFECTOR's approach in targeting selective translation regulators is unique, and eFT508 represents a promising novel class of investigational compounds for the treatment of cancer. Given the preclinical data already developed with eFT508 and checkpoint inhibitors, we are excited to initiate this joint clinical collaboration."