The companies plan to initiate a Phase 2 open-label, randomized, non-comparative study to evaluate the safety, tolerability and efficacy of eFFECTOR’s investigational small molecule MNK1/2 inhibitor, eFT508, in combination with avelumab in microsatellite stable relapsed or refractory CRC patients.
Avelumab is currently under clinical evaluation across a broad range of tumor types by the global strategic alliance between Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD Serono, and Pfizer.
The study will also include a monotherapy arm investigating eFT508 alone. Patients will be randomized 2:1 between the combination arm and the monotherapy arm.
“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 chief executive officer of eFFECTOR.
“We are very pleased to be working with Pfizer and Merck KGaA, Darmstadt, Germany, given their demonstrated commitment to develop avelumab as a leading checkpoint inhibitor and their deep knowledge in the field of immuno-oncology.”
eFT508 and avelumab are part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system in fighting cancer. eFT508 is a novel, oral immuno-oncology therapeutic that is a highly selective inhibitor of MNK1/2 kinases that mediate tumor immune evasion and are activated downstream of MEK and MAPK signaling.
Avelumab is a human programmed death ligand-1 (PD-L1) blocking antibody that is designed to potentially engage both the adaptive and innate immune systems. The collaboration builds upon promising preclinical data providing a scientific rationale for combining eFT508 with checkpoint inhibitors presented at recent clinical and scientific conferences.
In immunocompetent in vivo models, eFT508 induced anti-tumor immunity and immune memory as a single agent and, importantly for this collaboration, acted synergistically in combination with checkpoint inhibitors.
eFFECTOR has presented preclinical data at scientific conferences that eFT508 may play an important role in coordinately activating an anti-tumor immune response by selectively inhibiting several immuno-suppressive mechanisms while simultaneously stimulating several immunity-inducing mechanisms.
Immuno-suppressive mechanisms selectively inhibited by eFT08 include PD-1, LAG3, PD-L1 and IL-10, while pro-immunity mechanisms stimulated by eFT08 include antigen presentation, dendritic cell activation, effector T-cell function and expansion of the T-cell central memory pool.
“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,” said Chris Boshoff, M.D., Ph.D., Senior Vice President 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.”
“Colorectal cancer is a frequently diagnosed cancer and is the second most common cause of cancer death among men and women combined in the US,” said Alise Reicin, Head of Global Clinical Development at the biopharma business of Merck KGaA, Darmstadt, Germany. “New and innovative treatment strategies are desperately needed. 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 colorectal cancer.”
The study, which is expected to begin in the third quarter of 2017, will be conducted by eFFECTOR Therapeutics. Pfizer and Merck KGaA, Darmstadt, Germany, will share the clinical study costs with eFFECTOR. Each party will provide their respective agent for the trial.
Avelumab is under clinical investigation for treatment of microsatellite stable colorectal cancer and has not been demonstrated to be safe and effective for this indication. There is no guarantee that avelumab will be approved for microsatellite stable colorectal cancer by any health authority worldwide.