Combinability of X4P-001-IO with Nivolumab Demonstrated in ccRCC Shows Promise

At the 16^th Annual Meeting of the Association for Cancer Immunotherapy (CIMT) in Mainz, Germany, X4 Pharmaceuticals released data from a pilot study of X4P-001-IO in combination with Opdivo (nivolumab) in patients with clear cell renal cell carcinoma (ccRCC) who are non-responsive to the anti-PD-1 checkpoint inhibitor nivolumab alone.

X4P-001-IO is a CXCR4 inhibitor that uses a patient’s own immune system to combat cancer. Nivolumab is a targeted therapy that is a human programmed death receptor-1 (PD-1) blocking antibody.

As of February 26, 2018, 9 patients with advanced ccRCC were enrolled in the pilot study. All participating subjects received standard bi-weekly nivolumab therapy and X4P-001-IO (400 mg, oral, once daily) with 3.7 (range 1 to 10 months) months being the median duration of treatment with the combination. All subjects were non-responsive to single agent nivolumab with either a stable or progressive disease.

David F. McDermott, MD, Beth Israel Deaconess Medical Center, Harvard Medical School and lead investigator of the study commented on the pilot study’s promising findings in a recent statement. “These data demonstrate that the combination with X4P-001-IO and nivolumab has the potential to augment responses in patients who previously received the anti-PD-1 checkpoint inhibitor nivolumab alone,” he said. “This preliminary data requires validation in larger studies as we continue to seek treatments to address the larger population of cancer patients who do not adequately respond to checkpoint inhibitors.”

Investigators noted that X4P-001-IO in combination with nivolumab had acceptable toxicity. The most frequent adverse events were diarrhea, nasal congestion, dry eye, headache, and cough. However, all grade 3/serious adverse events were manageable with appropriate intervention; grade 4 and 5 adverse events did not occur.

The combination therapy also exhibited anti-tumor activity in some patients with advanced ccRCC who were previously non-responsive to single agent nivolumab therapy. Of these patients, 4 who had improved on prior nivolumab monotherapy experienced a best response of stable disease with additional X4P-001-IO treatment. Furthermore, 1 of the 5 patients who were stable on prior nivolumab monotherapy experienced a partial response with combination therapy.

“These findings contribute to our growing understanding of combining CXCR4 antagonists with other agents such as checkpoint inhibitors,” added Sudha Parasuraman, MD, Chief Medical Officer of X4 Pharmaceuticals. “Because the mechanisms of CXCR4 antagonism and check point inhibition act at different points in the tumor immunity cycle, it is reasonable to consider the potential for synergistic activity.”

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