ATLANTA — Use of the novel CD40 agonist APX005M with or without nivolumab (Opdivo) led to responses in more than half of patients with metastatic pancreatic cancer on first-line chemotherapy, results of a phase Ib found.
Among 24 patients with untreated metastatic disease, 13 achieved a partial response to the chemotherapy-immunotherapy combination and an additional nine had stable disease, Mark O’Hara, MD, of the University of Pennsylvania in Philadelphia, reported here at the American Association for Cancer Research annual meeting.
“Those numbers, while it’s a very small population, are very encouraging,” O’Hara told MedPage Today. “The response rate was 54%, which is much higher than what we’d anticipate with pancreatic cancer, and the disease control rate was 92%.”
Past chemotherapy trials in metastatic pancreatic cancer have had modest rates of response and disease control. In 171 patients treated with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), 32% responded and the disease control rate was 70%.
In a 2013 study of 431 patients treated with gemcitabine (Gemzar) and nab-paclitaxel (Abraxane), the standard chemotherapy used in the current study, 23% responded while the rate of disease control was 48%. And in a recent phase I study, adding nivolumab did not appear to lead to further gains, with rates of 18% and 64%, respectively.
APX005M is an agonist of CD40, which is present in both cancer and immune cells, and engaging with CD40 primes and activates antigen presenting cells and leads to stimulation of the immune system, O’Hara explained. Pancreas cancer models in the lab showed that adding APX005M to gemcitabine/nab-paclitaxel increased T-cell dependant tumor destruction in mice, which led the researchers to add nivolumab, and the four-drug combination improved survival in mice with pancreatic cancer.
….The study was sponsored by the Parker Institute for Cancer Immunotherapy in collaboration with the Cancer Research Institute, Apexigen, and Bristol-Myers Squibb (BMS). Some co-authors are employees of Apexigen, which developed APX005M.