The FDA has unveiled Project Orbis, a program to review and approve cancer drugs in concert with international partners. As part of the project, the FDA and its counterparts in Australia and Canada simultaneously approved a new treatment for advanced endometrial cancer.
The project can “help make potentially life-changing treatments available to patients as quickly as possible while still ensuring the FDA’s high standards of safety and effectiveness,” said Acting FDA Commissioner Ned Sharpless, MD, who expects to add more international partners. Differing global standards of care affect the increasingly international conduct of cancer clinical trials, potentially slowing the development of anticancer products. Project Orbis sets up a framework for concurrent submission and review.
As its first decision under Project Orbis, in conjunction with decisions by the Australian Therapeutic Goods Administration and Health Canada, the FDA granted accelerated approval to lenvatinib (Lenvima, Eisai Inc.) in combination with pembrolizumab (Keytruda, Merck) for the treatment of advanced endometrial carcinoma that is not microsatellite instability-high or mismatch repair deficient. The approval applies to patients who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation.
The approval was based on a trial in 94 patients. Ten patients (10.6% of responders) had a complete response, or disappearance of all lesions on imaging, and 26 patients (27.7% of responders) had a partial response, or shrinkage of lesions by at least 30%, for an objective response rate of 38.3%. The duration of response was greater than six months in 25 patients (69% of responders).
Common side effects included fatigue, high blood pressure, musculoskeletal pain, diarrhea, decreased appetite, hypothyroidism, nausea, and stomatitis. Additional side effects included vomiting, decreased weight, abdominal pain, headache, constipation, urinary tract infection, dysphonia, hemorrhagic events, hypomagnesemia, palmar-plantar erythrodysesthesia, dyspnea, cough, and rash. The drug combination may cause harm to a developing fetus or newborn baby.
The application received priority review and breakthrough therapy designations. Under the FDA’s “Real-Time Oncology Review” pilot program, which streamlines the submission of data, the decision took place three months prior to the FDA goal date. Since the regimen received accelerated approval, the sponsor must provide additional data to the FDA.
Source: FDA, September 17, 2019