Combination Immunotherapy Shows Early Promise Against Kidney, Lung Cancer

September 29, 2016

Combining two cancer immunotherapies to target both the interleukin 10 (IL-10) and programmed cell death protein 1 (PD-1) receptors has yielded promising early results for some patients with renal cell carcinoma and non-small cell lung cancer.

Combining two cancer immunotherapies to target both the interleukin 10 (IL-10) and programmed cell death protein 1 (PD-1) receptors has yielded promising early results for some patients with renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC), according to authors of a small multicohort phase Ib clinical trial.

The findings were reported at the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, held Sept. 25-28 in New York. The study is part of an emerging wave of clinical trials that are evaluating combinatorial immunotherapies against cancers.

“In this clinical trial, we found that the two immunotherapies were well-tolerated, without overlapping toxicity or severe autoimmunity, while providing strong antitumor responses,” said Aung Naing, MD, associate professor of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, in an American Association for Cancer Research news release.

Dr. Naing also reported detection of new, expanding T-cell clones in patients following AM0010 administration.

AM0010 is a PEGylated recombinant version of interleukin 10 (IL-10), an anti-inflammatory human cytokine. It showed promising preclinical antitumor activity and is now under investigation in human cancer clinical trials. It stimulates cytotoxic CD8+ T-cell activation, proliferation, and survival.

“Many of those T-cell clones were not detectable before treatment,” he noted. “This is reminiscent of tumor-specific vaccination.”

The study enrolled 19 patients with RCC, melanoma, and NSCLC for treatment with the investigational cytokine AM0010 and the immune PD-1 checkpoint inhibitor pembrolizumab (Keytruda), a humanized antibody that blocks the immune checkpoint inhibitor PD-1 receptor. It counteracts tumors’ suppression of T cells’ antitumor activity.

AM0010 administration was followed by elevations in patients’ serum levels of cytotoxic granzymes, FasL, and lymphotoxin beta. After 10 to 15 months of follow-up, complete responses (CRs) were seen in two of eight patients with RCC, and two other patients with RCC had partial responses (PRs). Two of six melanoma patients had PR and two other patients experienced pseudoprogression, a familiar phenomenon in immunotherapy involving initial tumor growth followed by declines in tumor volumes. Response rates were not reported in a news release for the study’s five patients with NSCLC.

Side effects associated with AM0010 included “manageable” anemia, thrombocytopenia, and fatigue, but did not include autoimmune problems, the authors reported.

Several other clinical cancer trials are currently under way to evaluate other combinatorial immunotherapies where monoimmunotherapy approaches have fallen short.

“Immunotherapy has improved the prospects for many cancer patients by providing long-term benefit, but not all patients respond to the currently available immuno-oncology drugs,” noted Dr. Naing. “Rational combinations of immune therapies are likely to expand the tumor-specific immune activation and lead to more durable tumor responses.”