Date: 2014-06-02
Type of information: Initiation of preclinical development
phase: 2
Announcement: presentation of results at the 50th American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 to June 3, 2014, in Chicago
Company: Incyte (USA)
Product: ruxolitinib
Action
mechanism: Ruxolitinib is an oral, selective inhibitor of Janus kinases 1 and 2 (JAK1 and JAK2). In the United States, ruxolitinib, brand name Jakafi®, is indicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. Jakafi® is marketed by Incyte in the United States and by Novartis as Jakavi® (ruxolitinib) outside the United States .
Disease: second-line metastatic pancreatic cancer
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The Ruxolitinib Efficacy and safety in combination with CApecitabine for subjects with recurrent or treatment refractory metastatic Pancreatic cancer (RECAP) trial was a Phase II, randomized, double-blind, placebo-controlled, proof-of-concept trial that investigated ruxolitinib in combination with capecitabine compared to capecitabine alone as treatment for metastatic pancreatic cancer. The trial was designed, in part, to characterize patients with metastatic pancreatic cancer who may benefit from JAK pathway inhibition with ruxolitinib therapy. An open-label, run-in period was included to assess the safety of ruxolitinib plus capecitabine in a cohort of nine patients. After completion of this run-in period, the randomized, double-blind portion of the study was conducted. One hundred twenty seven patients were randomized to one of two treatment arms: ruxolitinib 15 mg twice daily plus capecitabine 2000 mg/m2, as 1000 mg/m2 twice daily (n=64) or placebo plus capecitabine 2000 mg/m2, as 1000 mg/m2 twice daily (n=63). Oral ruxolitinib or placebo was self-administered every day of each 21-day cycle. Capecitabine was self-administered for the initial 14 days of each cycle. The primary endpoint of RECAP was overall survival measured from the time of randomization to the occurrence of death or discontinuation.
Latest
news: * On June 2, 2014, Incyte Corporation 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. 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.
