Study conducted in collaboration with Merck KGaA, Darmstadt, Germany, and Pfizer
SAN DIEGO, October 4, 2017 – eFFECTOR Therapeutics, Inc., a leader in the development of selective translation regulators (STRs) for the treatment of cancer, today announced it has initiated dosing in a Phase 2 clinical study of eFT508 in combination with avelumab* in microsatellite stable colorectal cancer (MSS CRC). The trial (NCT03258398) is being conducted under a clinical collaboration and supply agreement announced earlier this year between eFFECTOR and a global strategic alliance of Pfizer and Merck, KGaA, Darmstadt, Germany.
“eFT508 promotes anti-tumor immune response and we believe it has the potential to improve patient outcomes when used as a single agent or in combination with other immuno-oncology drugs, such as avelumab, an anti-PD-L1 checkpoint inhibitor,” said Steve Worland, Ph.D., president and chief executive officer of eFFECTOR. “We’ve demonstrated that eFT508 is well-tolerated as a single agent in patients with refractory solid tumors in a Phase 1 study. The newly initiated trial represents the first of several Phase 2 trials we plan to conduct with eFT508. We anticipate reporting interim response data from this trial in mid-2018.”
The open-label, randomized, non-comparative study is designed to evaluate the efficacy, safety and tolerability of eFFECTOR’s oral, small molecule MNK1/2 inhibitor eFT508 in combination with avelumab, a human anti-PD-L1 IgG1 monoclonal antibody. In addition to the combination arm, it also includes a monotherapy arm of eFT508. The multicenter study is being conducted in the U.S. and includes an initial assessment of the safety and tolerability of escalating doses of eFT508 in combination with avelumab, after which additional patients will be randomized to either the combination or eFT508 alone. Interim data from the first 20 patients in the randomized portion of the study are expected in mid-2018.
Avelumab has received accelerated approval** by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and previously treated patients with locally advanced and metastatic urothelial carcinoma, and is under further clinical evaluation across a range of tumor types under a global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer.
*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.
About the eFT508 Phase 2 Combination Study with Avelumab
This trial is a Phase 2, open-label, 2-part, multicenter study in subjects with MSS relapsed or refractory colorectal cancer. The primary objective of part 1 is to evaluate the safety and tolerability of escalating doses of eFT508 in combination with a fixed dose of avelumab to determine the maximum-tolerated dose (MTD) of eFT508 in combination with avelumab and to select a recommended dose for part 2. The primary objective of part 2 is to evaluate the antitumor activity of eFT508 at the recommended dose in combination with avelumab or as monotherapy.
Study therapy will be administered in 4-week treatment cycles. eFT508 will be taken orally twice a day and avelumab 10 mg/kg will be administered intravenously every 2 weeks. All subjects are expected to have tumor biopsies taken pre- and on-treatment to allow assessment of pharmacodynamic markers of activity and potential biomarkers of eFT508 sensitivity. Patients who experience disease progression on eFT508 alone will be eligible to add avelumab to their treatment.
The study will be conducted at 6 to 10 centers in the U.S. by eFFECTOR Therapeutics. Pfizer and Merck KGaA, Darmstadt, Germany, will share the clinical study costs with eFFECTOR and each party will provide their respective agent for the trial.
eFT508 is a selective translation regulator and is 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 highly potent and selective, oral inhibitor of MNK1 and MNK2. MNK1/2 are terminal kinases in key oncogenic signaling pathways, including KRAS-BRAF-MEK-ERK, and are activated by the mitogen dependent protein kinases (MAPK) in multiple immune cell types. MNK1 and MNK2 integrate MAPK pathway signaling at the level of mRNA translation, resulting in decreased anti-tumor immune activity due to selective upregulation of several immune checkpoint receptors and specific immunosuppressive cytokines. eFT508 selectively blocks MNK1/2 driven mRNA translation, thereby promoting anti-tumor immune response. eFT508 is currently being evaluated in a Phase 1/2 clinical trial in patients with solid tumors (NCT02605083) and in a Phase 1/2 clinical trial in patients with lymphoma (NCT02937675).
Avelumab is a human antibody specific for a protein called PD-L1, or programmed death ligand-1. Avelumab is designed to potentially engage both the adaptive and innate immune systems. By binding to PD-L1, avelumab is thought to prevent tumor cells from using PD-L1 for protection against white blood cells, such as T cells, exposing them to anti-tumor responses. Avelumab has been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.
**Indications in the US
The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO®) for the treatment of (i) mMCC in adults and pediatric patients 12 years and older and (ii) patients with locally advanced or metastatic urothelial carcinoma (UC) who have disease progression during or following platinum-containing chemotherapy, or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications were approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
Important Safety Information
The warnings and precautions for avelumab (BAVENCIO®) include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO for mMCC and patients with locally advanced or metastatic UC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.
For full prescribing information and medication guide for BAVENCIO, please see www.BAVENCIO.com.
Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables the companies to benefit from each other’s strengths and capabilities and further explore the therapeutic potential of avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab and advance Pfizer’s PD-1 antibody. The alliance is focused on developing high-priority international clinical programs to investigate avelumab as a monotherapy, as well as in combination regimens, and is striving to find new ways to treat cancer.
About eFFECTOR Therapeutics
eFFECTOR Therapeutics is a clinical-stage biopharmaceutical company pioneering the discovery and development of selective translation regulators as a new class of small molecule therapeutics for cancer. The company’s investigational compounds are designed to restore translational control to halt underlying disease mechanisms while preserving healthy physiological processes. eFFECTOR’s most advanced program focuses on the development of eFT508. The company has additional selective translation regulator programs currently in discovery and development and maintains global rights to all of its development programs. For more information visit www.effector.com.
Robert H. Uhl
Heidi Chokeir, Ph.D.