Zev Wainberg, MD
The combination of the novel tumor-associated macrophage (TAM)-targeting agent cabiralizumab and the PD-1 inhibitor nivolumab (Opdivo) resulted in intriguing objective response rates in heavily pretreated patients with metastatic pancreatic cancer, according to findings from a phase I study presented at the 2017 SITC Annual Meeting.
Efficacy findings were presented solely for patients with pancreatic cancer at the SITC meeting, although adverse events (AEs) were described across the full study. The pancreatic cancer cohort contained 33 patients treated in the dose expansion stage of the study. The median age was 64 years, 58% had ECOG PS of 1, and 45% had received ≥3 prior regimens.
In the pancreatic cancer group, the most common treatment-related AEs (TRAEs) of all grades were serum enzyme elevations (52%), fatigue (42%), periorbital edema (30%), rash (21%), and vomiting (21%). The most common grade 3/4 TRAEs were serum enzyme elevations (33%), hyponatremia (9%), and rash maculopapular (9%). AEs led to treatment discontinuation for 9% of patients, all of which were grade 3/4 in severity.
Across all patients treated with the combination, the most common grade 3/4 TRAEs were serum enzyme elevations (20%), pancreatic enzyme elevations (12%), fatigue (5%), rash (4%), pruritus (1%), and periorbital edema (<1%). There were 3 treatment-related deaths in the combination arm, these were due to pneumonitis in a patient with thyroid cancer (n = 1) and respiratory distress (n = 1) and acute respiratory distress (n = 1) in patients with lung cancer. The most frequently observed grade 3/4 TRAEs with cabiralizumab monotherapy were serum enzyme elevation (38%), pancreatic enzyme elevations (8%), and rash (4%).
"The most common treatment-related AEs were elevations in creatine kinase and serum liver enzymes, without elevation in bilirubin," said Wainberg. "These are believed to be secondary to cabiralizumab’s depletion of macrophages and might represent a class effect of CSF-1R inhibition. Isolated serum enzyme elevations were not associated with other clinical presentation."
A phase II study is currently enrolling to explore the combination of cabiralizumab and nivolumab with or without chemotherapy for patients with advanced pancreatic cancer. Chemotherapy agents in the trial will consist of nab-paclitaxel (Abraxane), gemcitabine, irinotecan liposome injection (Onivyde), or the FOLFIRINOX chemotherapy. The primary endpoint of the study, which plans to enroll 160 patients, is progression-free survival (NCT03336216).
Wainberg ZA, Piha-Paul SA, Luke JJ, et al. First-in-Human Phase 1 Dose Escalation and Expansion of a Novel Combination, Anti–CSF-1 Receptor (cabiralizumab) Plus Anti–PD-1 (nivolumab), in Patients With Advanced Solid Tumors. Presented at: 32nd SITC Annual Meeting; November 8-12, 2017; National Harbor, MD. Abstract O4
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