Immune-stimulating Drug and Chemotherapy Show Early Promise for Pancreatic Cancer
A phase 1b clinical trial indicated an experimental therapy for pancreatic cancer can sufficiently control tumors to make some patients eligible for surgery.1
Pancreatic cancer almost always affects people older than 40, and the most common type is pancreatic adenocarcinoma. The prognosis for pancreatic cancer is poor, in particular because diagnosis often occurs at a late stage. Though surgery provides the best chance for survival of pancreatic cancer, many patients are ineligible because their tumors are not sufficiently controlled.
The study, published in The Lancet Oncology, treated 47 patients diagnosed with locally advanced pancreatic ductal adenocarcinoma between April 2012 and November 2014. Treatment was with a standard, 4-drug chemotherapy alone (FOLFIRINOX, 8 patients) or FOLFIRINOX and an experimental, immune-stimulating drug called PF-04136309 (39 patients).
The target of PF-04136309 is CCR2 on inflammatory monocytes. CCR2 can allow cancerous cells to evade detection by the immune system, making it easier for cancerous cells to grow and spread.
Of the patients who completed the trial with PF-04136309 (33 patients), local tumor control was achieved in 32 (97%) of them. In the PF-04136309 arm, 16 (49%) achieved an objective tumor response. One patient receiving PF-04136309 experienced a compete disappearance of tumors.
Patients in the PF-04136309 arm experienced nearly double the response rate of patients receiving chemotherapy alone. In the FOLFIRINOX alone arm, 5 patients received repeat imaging, though none of them achieved an objective response. Four (80%) of the 5 did achieve stable disease.
No treatment-related deaths occurred. The majority of side effects with PF-04136309 were similar to side effects with chemotherapy alone, though 3 patients in the PF-04136309 arm withdrew due to treatment toxicity.
Researchers also confirmed that PF-04136309 effectively blocked its target, CCR2.
“In summary, PF-04136309 in combination with FOLFIRINOX did not result in additional toxicity at the recommended phase 2 dose. CCR2 blockade led to a reduction in the infiltration of tumor-associated macrophages and showed evidence of an endogenous antitumor immune response,” concluded the authors.
“Our results strongly suggest that CCR2-targeted therapy affects the biology of pancreatic ductal adenocarcinoma and future clinical trials should explore this promising therapeutic strategy.”
The researchers are planning a larger, randomized, phase 2 trial with Pfizer to assess PF-04136309 in patients with metastatic disease and prognoses to survive 6 to 12 months. Pfizer is the manufacturer of PF-04136309.
1. Nywening TM, Wang-Gillam A, Sanford DE, et al. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol. [Published online ahead of print April 4, 2016]. doi:10.1016/S1470-2045(16)00078-4.