RO4929097 Safe, Active in Refractory Metastatic or Locally Advanced Solid Tumor
In the multinational phase 1 study, patients received escalating doses of RO4929097 orally on two schedules: (A) 3 consecutive days/week for 2 weeks every 3 weeks; and (B) 7 consecutive days every 3 weeks.
An expanded part of the study assessed reversible CYP3A4 autoinduction by testing three dosing schedules: B, as above; modified A, 3 consecutive days/week for 3 weeks; and C, continuous daily dosing. The investigators assessed tumor metabolic effects using FDG-PET scans.
A total of 302 cycles of RO4929097 was administered to 58 patients on schedule A, 47 on schedule B, and 5 patients on schedule C, the expanded cohort. One patient with colorectal adenocarcinoma with neuroendocrine features had a partial response; 1 patient with sarcoma had a mixed response (stable disease); and 1 patient with melanoma had a nearly complete FDG-PET response. An effect on CYP3A4 induction was observed.
Fatigue, thrombocytopenia, fever, rash, chills, and anorexia were commonly observed grade 1 to 2 toxicities. Transient grade 3 hypophosphatemia (dose-limiting toxicity) was observed at 27mg in 1 patient and grade 3 pruritus in 2 patients at 60mg; on schedule A at 80mg, 1 patient had transient grade 3 asthenia. The investigators found RO4929097 270mg on schedule A and 135mg on schedule B to be well tolerated; safety of schedule C has not been fully evaluated.
“In conclusion, RO4929097 was well tolerated when administered by using both intermittent and continuous dosing schedules,” the investigators wrote. Several Cancer Therapy Evaluation Program-sponsored phase 1/2 studies are exploring the safety and efficacy of RO4929097, both alone and in combination. “Most of these studies use the three-on/four-off schedule at a starting dose of 20mg, which is a dose expected to not result in significant autoinduction and potential drug-drug interaction in this schedule. Recruitment on most of these studies is ongoing and results are awaited with interest,” they concluded.