First Patient Enrolled in Phase 1 Trial Investigating Galinpepimut-S and Opdivo for MPM

First Patient Enrolled in Phase 1 Trial Investigating Galinpepimut-S and Opdivo for MPM

Investigators enrolled the first patient in a Phase 1 clinical trial to evaluate the effects of the cancer vaccine  galinpepimut-S in combination with immune checkpoint inhibitor Opdivo (nivolumab) as a treatment for malignant pleural mesothelioma (MPM).

MPM, the most common type of malignant mesothelioma, is a cancer of the protective lining of the lungs (pleura), and is mostly caused by asbestos exposure. Patients are often treated with a combination of chemotherapy, radiotherapy, and surgery. But this usually leads to only minor improvements in survival rates.

Galinpepimut-S, developed by Sellas Life Sciences, has shown promise in MPM patients. It targets the Wilms tumor 1 (WT1) protein, found at high levels in several cancers and considered the number one target for cancer immunotherapy by the National Cancer Institute.

The vaccine was assessed in a randomized Phase 2 trial (NCT01890980), which found it led to sustained immune responses against WT1 and extended patients’ overall survival to 22.8 months, compared with 18.3 months with placebo.

Cancers like mesothelioma produce proteins that prevent immune cells from doing their job, suggesting that therapies that block these proteins could improve the efficacy of cancer vaccines such as galinpepimut-S.

Opdivo, by Bristol-Myers Squibb, is an immune checkpoint inhibitor that works by blocking the PD-L1 protein on cancer cells, preventing its binding to the PD-1 protein on T-cells — immune cells with the ability to fight tumors. By preventing this interaction, Opdivo helps the immune system regain its ability to find and eliminate cancer cells.

“There is significant preclinical and translational science evidence that PD-1 inhibitors may enhance the anti-cancer activity of cancer vaccines, with immuno-biologic and pharmacodynamic synergy from the combination of two such agents,” Marjorie G. Zauderer, MD, the principal investigator on the trial, said in a press release.

“By mitigating the negative effects of tumor microenvironment factors on immune response, PD-1 inhibitors, such as nivolumab, potentially allow for a patient’s immune cells to destroy cancerous growths that may be sensitized by GPS against WT1,” said Zauderer. “I believe that WT1 serves as an ideal target for directly immunizing therapies in MPM, and I look forward to evaluating the combination of GPS and nivolumab in the clinic.”

The ongoing, open-label, investigator-sponsored Phase 1 trial (NCT04040231) will investigate Opdivo in combination with galinpepimut-S in people with malignant pleural mesothelioma who are positive for the WT1 protein and have received at least one prior course of chemotherapy containing Alimta (pemetrexed).

Researchers are recruiting a total of 10 patients at six Memorial Sloan Kettering Cancer Center sites in New York and New Jersey.

Patients enrolled in the study will receive galinpepimut-S and Opdivo as a vaccine for 16 weeks, except at the starting point and week 2, at which points they will get galinpepimut-S vaccine alone. Patients will also receive injections of Leukine (sargramostim) under the skin two days per week.

Leukine is also designed to boost immune system activity. It acts by stimulating the bone marrow to produce more white blood cells — the main cell type of the immune system — and is typically given to patients to restore cell numbers following chemotherapy.

The primary goal of the trial is to determine the tolerability of the combination treatment. If more than two of the 10 participants experience severe reactions to the combination, it will not be considered tolerable in MPM patients.

Researchers will also monitor the proportion of patients who experience a lessening in tumor burden in response to treatment — the overall response rate (ORR) — and compare it to the ORR in similar MPM patients who received Opdivo in previous clinical trials.

“There are few effective therapies for mesothelioma, a disease which is characterized by high expression of the WT1 antigen, and we believe that the combination of GPS and nivolumab could be promising for patients with MPM, due to the combination’s potential synergistic immune-based mechanisms for anti-tumor activity,” said Angelos Stergiou, MD, president and CEO of Sellas. “We look forward to gaining further insights on the safety and clinical outcomes of this combination in MPM.”

Galinpepimut-S has been the subject of a number of clinical trials in patients with different forms of cancer, and received fast track status from the U.S. Food and Drug Administration (FDA) for MPM treatment in 2016.

“We are pleased to be collaborating with Memorial Sloan Kettering on this Phase 1 trial, and excited to have expanded the clinical evaluation of GPS in combination with nivolumab to patients with advanced MPM,” said Stergiou.