Phase 2 Trial to Test Keytruda, Tomivosertib Combo in Triple-negative Breast Cancers

Phase 2 Trial to Test Keytruda, Tomivosertib Combo in Triple-negative Breast Cancers

An upcoming Phase 2 trial will evaluate a combination of the immunotherapies Keytruda (pembrolizumab) and tomivosertib (eFT508) as a treatment for triple-negative breast cancer patients whose disease has spread to other regions, or metastasized.

As part of a new collaboration between eFFECTOR Therapeutics and Merck (known as MSD outside the U.S. and Canada), the trial will test the combination in women who have failed up to two prior treatments. Enrollment is expected to begin in early 2019.

“The TNBC trial will expand the current tomivosertib Phase 2 clinical trial program, allowing eFFECTOR to explore a combination with Keytruda for an indication in which neither drug is yet approved,” Steve Worland, PhD, president and CEO of eFFECTOR, said in a press release.

In an attempt to prevent the immune system from attacking the body’s own cells and tissues, immune cells are equipped with a series of checkpoint molecules that prevent them from becoming overactive.

Cancer cells often take advantage of this mechanism and produce molecules that activate these checkpoints, preventing immune cells from detecting and eliminating them.

Many immune checkpoint inhibitors are already approved for cancer indications, including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Yervoy (ipilimumab).

Tecentriq, an inhibitor of the PD-1 checkpoint protein, has already shown benefits in a quarter of triple-negative breast cancer patients included in a Phase 2 trial (NCT02447003).

Tomivosertib, on the other hand, is an inhibitor of the MNK1 and MNK2 proteins, two molecules that play a key role in cancer signaling pathways. Inhibiting these proteins reduces the amount of checkpoint molecules and other immunosuppressive molecules.

The multicenter Phase 2 trial will primarily evaluate the proportion of patients who achieve a response to the combination. Secondary measures include duration of responses, disease control rate, overall survival, and time until disease progression or death.

These parameters will be determined using the RECIST v1.1 and iRECIST, response evaluation criteria for solid tumors, with interim and final analyses at eight and 12 months after the last patient dosing.

“Based on preclinical studies showing tomivosertib has substantial immunomodulatory activity and synergizes with checkpoint inhibitors, we believe targeting MNK1/2 has significant potential to enhance the clinical activity of Keytruda,” Worland said.

Tomivosertib is also being examined as a stand-alone treatment for diffuse large B-cell lymphoma (NCT02937675), and in combination with immune checkpoint inhibitors in colorectal cancer (NCT03258398) and in patients who failed prior checkpoint blockade (NCT03616834).