Durable Responses Achieved with AM0010

In a phase Ib trial, a combination of the experimental immunotherapy AM0010 (ARMO Biosciences) and the immune checkpoint inhibitor pembrolizumab (Keytruda; Merck) was well tolerated and effective at controlling solid tumors in some patients with advanced disease. Data were presented at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference in New York, NY, at the end of September.

“Checkpoint inhibitors are bringing a sustained and dramatic response to some patients, but not all. Some patients respond initially, but later they progress,” said Aung Naing, MD, an associate professor in the department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center in Houston, who presented the findings. “There is room to improve, and to improve, we need to look at combination therapies.”

AM0010 is a PEGylated form of the recombinant human cytokine IL10. IL10 blocks NF-κB activity and activates the JAK–STAT3 signaling pathway, known to play a role in inflammation and innate immunity and, more recently, cancer initiation and progression. Research has also shown that IL10 stimulates antigen-mediated cytotoxicity and boosts the survival and proliferation of intratumoral CD8+ T cells. Because both the IL10 receptor and PD-1 are present on CD8+ T cells, Naing's team hypothesized that the AM0010–pembrolizumab combination could lead to improved tumor control.

Investigators enrolled 19 patients—eight with renal cell carcinoma (RCC), five with non–small cell lung cancer (NSCLC), and six with melanoma—to test the combination. After 10 to 15 months, two patients with RCC had a complete response and two others had their tumors shrink by 92% and 77%; median progression-free survival (PFS) was nearly 10 months and median overall survival (OS) had not yet been reached. Two patients with NSCLC also had partial responses to the treatment; median PFS was 9.3 months and median overall survival had not yet been reached. Two patients with melanoma experienced partial responses, and two others had an initial increase in tumor volume followed by a decrease, a phenomenon known as pseudoprogression. Survival data for these patients were not presented.

“We understand that this is a small number of patients,” commented Naing, “but our current plan is to expand to 30 patients with renal cell carcinoma and 30 patients with non–small cell lung cancer. We are also targeting melanoma patients who are refractory to the anti–PD-1 treatment.”

Naing reported that the side effects associated with the treatment—namely anemia, thrombocytopenia, and fatigue—were relatively mild and manageable. Most importantly, he noted that patients didn't experience any autoimmune reactions.

Analysis of blood samples from patients who responded to the drug duo provided additional evidence of immune system activation. For example, researchers found that several hundred T-cell clones per patient expanded more than 10-fold. Further, they discovered an increase in immune stimulatory cytokines, such as IFNγ, IL4, and IL18, as well as an increase in CD8 T-cell effector molecules, including FasL and lymphotoxin beta.

Based on the encouraging results, Peter Van Vlasselaer, PhD, president and CEO of ARMO Biosciences, said that the company plans to initiate a phase III study by the end of the year. –Suzanne Rose