A new study has shown a novel peptide antagonist, given in combination with a PD-1 inhibitor, to be safe and well-tolerated in patients with advanced, refractory pancreatic and rectal cancer. The highest dose tested had a good safety profile and was recommended for use in future patient trials, as reported in Journal of Pancreatic Cancer, a peer-reviewed open access publication from Mary Ann Liebert, Inc., publishers.

“Safety and Pharmacokinetics of CXCR4 Peptide Antagonist, LY2510924, in Combination with Durvalumab in Advanced Refractory Solid Tumors” was coauthored by Mark O’Hara, MD, Abramson Cancer Center at the University of Pennsylvania, and colleagues from University of Colorado School of Medicine, The University of Chicago Medicine, Eli Lilly and Company, Astra Zeneca, and Washington University Medical School in St. Louis.

The purpose of this open label phase 1a study was to determine the maximum tolerated dose, safety, and tolerability of LY2510924, a CXCR4 peptide antagonist with proven, significant antitumor activity in preclinical studies, given in combination with the PD-1 inhibitor durvalumab. The study patients had advanced pancreatic or rectal cancer that did not respond to other treatment. Patients received 20, 30, or 40 mg of LY2510924 daily together with 1500 mg of durvalumab on day 1 of each 28-day cycle. No adverse events resulted in death or the need to discontinue treatment with any of the three doses, leading to the conclusion that the highest dose of LY2510924, 40 mg, daily is safe and well-tolerated and should be used in the next phase of studies. The researchers also reported that a best response of stable disease was seen in 44% of patients in the trial.

Journal of Pancreatic Cancer Editor-in-Chief Charles J. Yeo, MD, Department of Surgery, Thomas Jefferson University, states:

The Journal was pleased to publish this phase 1 study using a CXCR4 peptide antagonist with a PD-1 inhibitor in eight patients with advanced pancreatic cancer. The combination yielded tolerable side effects and some patients showing a certain degree of disease stability.”

Journal reference:

O’Hara, M.H., et al. (2020) Safety and Pharmacokinetics of CXCR4 Peptide Antagonist, LY2510924, in Combination with Durvalumab in Advanced Refractory Solid Tumors. Journal of Pancreatic Cancer. doi.org/10.1089/pancan.2019.0018.

Source