Infinity Presents Positive Early Data on Therapy for NSCLC, Other Solid Tumors

Infinity Presents Positive Early Data on Therapy for NSCLC, Other Solid Tumors

Infinity Pharmaceuticals recently presented pre-clinical and clinical data from the company’s oral therapy candidate IPI-549 in solid tumors.

The data was presented during the plenary session “PI3K Pathways in Immunology, Growth Disorders and Cancer” at the Keystone Symposia Conference.

IPI-549 is an investigational immuno-oncology agent that selectively inhibits PI3K-gamma, a key enzyme in leukocyte signaling.

During the presentation, titled “The PI3K-gamma inhibitor, IPI-549, increases antitumor immunity by targeting tumor-associated myeloid cells and overcomes immune checkpoint blockade resistance in preclinical models,” Jeffery Kutok, MD, PhD, vice president of biology and translational science at Infinity Pharmaceuticals, reviewed the data for IPI-549.

In pre-clinical studies, IPI-549 has been shown to inhibit immunosuppressive macrophages within the tumor microenvironment (TME), which are often associated with resistance to immunotherapies like immune checkpoint inhibitors. The TME refers to the noncancerous cells in a tumor; these cells can provide growth signals to tumor cells, as well as signals that inhibit an anti-tumor immune response, according to an Infinity news release.

By switching these immunosuppressive macrophages into pro-inflammatory ones, IPI-549 could enhance T-cell activity, particularly when combined with checkpoint modulators, lab studies indicate.

Kutok also presented initial data from the dose-escalation Phase 1/1b clinical trial (NCT02637531), which was designed to evaluate the safety, tolerability, and drug properties of IPI-549 as a monotherapy or in combination with Opdivo (nivolumab) in 175 patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), melanoma, and squamous cell carcinoma of the head and neck (SCCHN).

An Infinity release says there is a great need for additional treatment options for patients living with these cancers, which account for more than 17 percent of all new cancer cases in the U.S., according to the American Cancer Society.

Initial Phase 1 trial data from nine patients taking part in the dose-escalation part of the trial found no dose limiting toxicities and no serious adverse events. The patients were administered IPI-549 as a single therapy at doses from 10 mg once daily to 20 mg once a day.

“While new immunotherapies, such as T-cell checkpoint inhibitors, are showing great promise in the treatment of various cancers, there are multiple mechanisms of immune tolerance in tumors,” Kutok said. “Additional treatment options are needed for patients who relapse or do not respond to currently available therapies.”

Kutok said the data suggests that targeting PI3K-gamma with the drug candidate IPI-549 within immune-suppressive myeloid cells could be an innovative method to “enhance the activity of checkpoint inhibition in sensitive tumors as well as to overcome tumor resistance to checkpoint inhibition.”

He said Infinity will report additional data from its Phase 1 study of IPI-549 later this year.

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