First Patients Dosed in Phase 1/2 Trial Testing Galinpepimut-S, Keytruda Combo in Advanced Cancers

A Phase 1/2 clinical trial assessing the cancer vaccine galinpepimut-S in combination with Keytruda (pembrolizumab) as a treatment for WT-1-positive advanced cancers has started dosing patients, Sellas Life Sciences announced.

Galinpepimut-S is a cancer vaccine developed by Sellas to target the Wilms tumor 1 (WT1) protein. WT1 is found at high levels in several cancers and is considered the No. 1 target for cancer immunotherapy by the National Cancer Institute.

Originally developed by researchers at the Memorial Sloan Kettering Cancer Center, galinpepimut-S consists of four small proteins that elicit a strong immune response against WT-1. It also creates a kind of immune memory, allowing the immune system to eliminate cancer cells that return after treatment.

Keytruda is a so-called immune checkpoint inhibitor, which works by blocking the interaction between the PD-1 protein on immune T-cells with the PD-L1 protein on cancer cells. Cancers often use this interaction to inhibit the function of immune cells, thus Keytruda works to boost the body’s own immune system.

When administered in combination, these therapies are thought to activate and stimulate the immune system to react against WT1 and destroy cancer cells.

The Phase 1/2 trial (NCT03761914), which is currently recruiting participants, expects to enrol 90 patients with WT1-positive relapsed or refractory tumors, including acute myeloid leukemia (AML), colorectal, ovarian, small-cell lung, and triple-negative breast cancers.

The study will begin to evaluate patients with ovarian cancer who failed one to two prior lines of treatment and colorectal cancer patients who received two to three prior therapies. Then it will assess the combination in AML patients who experienced no better than a partial response on hypomethylating agents and who are unable to receive a stem cell transplant, and in triple-negative breast and small-cell lung cancer patients who received one prior line of therapy.

The trial will be conducted in up to 20 centers in the U.S., some of which are still recruiting. More info is available here. The main goal of the trial is to determine the treatment’s safety, as assessed by the frequency of adverse events in all tumor types, the proportion of solid-tumor patients responding to treatment, and the proportion of AML patients achieving a complete response.

The trial will be led by Richard Maziarz, a medical director at the Knight Cancer Institute and professor of medicine at Oregon Health and Science University, and Roisin O’Cearbhaill, an assistant attending physician at the Memorial Sloan Kettering Cancer Center.

“This is an important milestone as this study allows us to potentially enhance our safety and activity profile of GPS [galinpepimut-S] in combination with anti-PD-1 therapies, particularly in combination with Keytruda in multiple malignances, following intriguing initial combination clinical data with Opdivo,” Angelos M. Stergiou, president and CEO of Sellas, said in a news release.

Results from a Phase 1 study with ovarian cancer patients showed that 70% of them lived for a year without signs of disease progression — a measure called progression-free survival — when treated with galinpepimut-S in combination with Opdivo (nivolumab), an anti-PD-1 therapy from Bristol-Myers Squibb. One-year progression-free survival with standard therapy typically does not exceed 50%.

“We are confident this study will build on our body of clinical evidence in support of the use of GPS in combination with PD-1 inhibitors to benefit cancer patients with limited treatment options,” Stergiou said.

“These beliefs are shared by the renowned U.S. oncologists who are undertaking this work. We look forward to studying this combination in patients with a wide range of cancers and expect to provide the first clinical data from this study in the first quarter of 2020,” he added.

Galinpepimut-S has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA), and the European Medicines Agency for AML, malignant pleural mesotheliomia, and multiple myeloma. The candidate therapy also received the FDA’s fast track designation for the same indications.