eFFECTOR Therapeutics, Pfizer, and Merck KGaA established a partnership to carry out Phase II study evaluating the safety, tolerability, and efficacy of eFFECTOR’s small-molecule investigational MNK1/2 (MAP kinase-interacting kinase 1 and 2) inhibitor eFT508 combined with Merck KGaA’s and Pfizer’s programmed death-ligand 1 (PD-L1) antibody avelumab (Bavencio®) in patients with microsatellite-stable relapsed or refractory colorectal cancer (CRC). eFFECTOR will conduct the noncomparative study, which is projected to start during the third quarter of this year, and will also include an eFT508 montherapy arm. Pfizer and Merck KGaA will share associated trial costs.
“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.
“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,” commented Alise Reicin, M.D., head of global clinical development at Merck KGaA.
eFT508 is designed as a highly potent, selective oral inhibitor of MNK1 and MNK2, which act as terminal kinases in key oncogenic signaling pathways. The drug is currently being evaluated in separate Phase I/II clinical trials in patients with solid tumors and with lymphoma. eFFECTOR says recently presented preclinical data indicate that eFT508 induces antitumor immunity and immune memory as a single agent and also acts synergistically in combination with checkpoint inhibitors. eFT508 was granted orphan drug designation by the FDA in March for the treatment of diffuse large B-cell lymphoma.
“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,” noted Chris Boshoff, M.D., Ph.D., svp and head of immuno-oncology, early development, and translational oncology, Pfizer Global Product Development. “Given the preclinical data already developed with eFT508 and checkpoint inhibitors, we are excited to initiate this joint clinical collaboration.”
San Diego, CA-based eFFECTOR was founded in 2012 to develop a new class of cancer-targeting selective translation regulators (STRs), based on technology developed at the University of California, San Francisco (UCSF). The firm’s preclinical pipeline includes eFT226, a selective small-molecule inhibitor of eIF4A, or eurkaryotic initiation factor 4A. eFFECTOR projects filing an IND application to the FDA for eFT226 by the end of 2017. The firm is also developing a series of small-molecule inhibitors of eIF4E, which it says is a historically intractable target that is inked with poor prognosis.
Pfizer and Merck KGaA set up their alliance to co-develop and co-commercialize avelumab back in 2014. In March this year, the FDA granted the antibody accelerated approval for treating metastatic Merkel cell carcinoma. Last month, the U.S. regulator approved avelumab for treating locally advanced or metastatic urothelial cell carcionoma. Avelumab is being evaluated in the JAVELIN clinical trial program, which includes at least nine Phase III studies in more than 15 tumor types.