Incyte Announces Full Results from Proof-of-Concept Phase II RECAP Trial of Jakafi® (ruxolitinib) in Combination with Capecitabine in Patients with Metastatic Pancreatic Cancer

Incyte Corporation INCY today announced full results from RECAP, a Phase II trial of ruxolitinib, a JAK1/JAK2 inhibitor, in combination with capecitabine in second-line metastatic pancreatic cancer. The findings from this proof-of-concept trial showed that ruxolitinib plus capecitabine prolonged survival over capecitabine alone in patients with elevated C-reactive protein (CRP), a well-established marker of systemic inflammation (hazard ratio = 0.47; 95% CI, 0.26-0.85; P=0.01 (2-sided)). Patients in this subgroup treated with ruxolitinib plus capecitabine also achieved improvements in other efficacy measures including objective response rate, clinical benefit response, and weight gain. These data were presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Systemic inflammation is commonly observed in patients with advanced malignancies and has been associated with poor survival.1,2 The majority of patients with pancreatic cancer exhibit evidence of systemic inflammation, which can be associated with weight loss, decreased muscle mass, and poor performance status.3 Elevated CRP, a well characterized, sensitive, and readily measurable marker of systemic inflammation, has negative prognostic significance in many human cancers, including pancreatic cancer.4,5,6,7 “Ruxolitinib in combination with capecitabine was generally well tolerated and exhibited greater clinical activity compared to capecitabine alone in patients with second-line metastatic pancreatic cancer and elevated CRP,” said Herbert Hurwitz, M.D., Professor of Medicine, Duke University School of Medicine, principal investigator of RECAP who presented the study findings. “Local and systemic inflammation adversely affect patient outcomes in pancreatic cancer and many other malignancies. The findings are very encouraging, especially given the limited treatment options for these patients.” The RECAP study enrolled 127 patients: 64 randomized to receive ruxolitinib plus capecitabine and 63 to capecitabine alone. In the intent-to-treat population, the hazard ratio for overall survival was 0.79 (95% CI, 0.53–1.18; P=0.25 (2-sided)). When patients with elevated CRP levels were evaluated (n=60), a pre-specified subgroup based on median CRP at study entry (13 mg/L), the hazard ratio for overall survival was 0.47 (95% CI: 0.26–0.85; P=0.01 (2-sided)). In this subgroup, the probability of survival in the ruxolitinib plus capecitabine group versus the capecitabine alone group at three, six, and 12 months was 48 percent, 42 percent, and 11 percent versus 29 percent, 11 percent, and 0 percent, respectively; the median time to death was 83 days in the ruxolitinib plus capecitabine group versus 55 days in the capecitabine alone group with greater differences between the treatment arms emerging after the median time to death. A post hoc analysis of overall survival was also conducted using the modified Glasgow Prognostic Score (mGPS), a well-characterized and prognostically relevant measure of inflammation in cancer.8 Among patients in the higher risk categories (mGPS = 1 or 2 corresponding to patients with CRP >10 mg/L), overall survival favored the ruxolitinib-capecitabine combination over capecitabine alone (HR = 0.60; 95% CI, 0.35-1.03; P=0.063 (2-sided)). Similar trends were observed in progression-free survival. The hazard ratio was 0.75 (95% Cl: 0.51–1.10; P=0.14 (2-sided)) in favor of ruxolitinib plus capecitabine in the intent-to-treat population, and 0.62 (95% CI: 0.35–1.10; P=0.10 (2-sided)) in the subgroup of patients with CRP > 13 mg/L. Benefits with ruxolitinib plus capecitabine treatment were also observed in objective response rate, clinical benefit response (a composite of improvement in pain intensity, Karnofsky performance status, analgesia, and weight), and weight gain. Treatment with ruxolitinib plus capecitabine was generally well tolerated. Grade ≥3 anemia occurred more frequently in patients treated with ruxolitinib plus capecitabine (15.3%) compared with those who received placebo plus capecitabine (1.7%). Grade ≥3 neutropenia and thrombocytopenia were uncommon in ruxolitinib-treated patients. Grade 3 or 4 non-hematologic adverse events that occurred more frequently with ruxolitinib plus capecitabine compared with placebo plus capecitabine included pulmonary embolism (11.9% vs 5.0%), stomatitis (6.8% vs 0%), and pneumonia (8.5% vs 1.7%). Differences in exposure between treatment groups (mean of 99.6 days for ruxolitinib plus capecitabine vs 67.4 days for capecitabine alone) may have contributed to the differences in the rates of adverse events. “RECAP provides the first evidence that targeting onco-inflammation through the JAK-STAT pathway with ruxolitinib may improve survival in patients with elevated CRP,” said Hervé Hoppenot, President and Chief Executive Officer, Incyte. “We have initiated a pivotal Phase III clinical program in patients with mGPS of 1 or 2 to confirm these findings in pancreatic cancer. We are also investigating the utility of ruxolitinib in other tumor types in which onco-inflammation plays a key role.” The slides used during the presentation can be accessed at 2014 ASCO - RECAP Presentation. Incyte's Phase III program in pancreatic cancer includes two double-blind, placebo-controlled trials focusing on patients with mGPS of 1 or 2 which is also defined as CRP >10 mg/L: JANUS 1 (NCT02117479) and JANUS 2 (NCT02119663). Clinical trials evaluating ruxolitinib activity using mGPS-based patient selection criteria are ongoing in other solid tumors (colorectal cancer (NCT02119676), non-small cell lung cancer (NCT02119650), and breast cancer (NCT02120417)).