The FDA ( U.S. Food and Drug Administration ) has announced Project Orbis, an initiative of the FDA Oncology Center of Excellence ( OCE ).
Project Orbis provides a framework for concurrent submission and review of oncology drugs among its international partners.
Under this project, the FDA, the Australian Therapeutic Goods Administration ( TGA ) and Health Canada collaboratively reviewed applications for two oncology drugs, allowing for simultaneous decisions in all three countries.
Collaboration among international regulators may allow patients with cancer to receive earlier access to products in other countries where there may be significant delays in regulatory submissions, regardless of whether the product has received FDA approval. This is partly due to different standards of care around the world that also have an impact on the increasingly international conduct of cancer clinical trials, potentially slowing the development of anticancer products. With a framework for concurrent submission and review of oncology drugs, Project Orbis facilitates a collaborative review to identify any regulatory divergence across review teams.
As part of Project Orbis, in conjunction with decisions by TGA and Health Canada, the FDA have granted accelerated approval to Lenvima ( Lenvatinib ) in combination with Keytruda ( Pembrolizumab ) for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high ( MSI-H ) or mismatch repair deficient ( dMMR ), and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation.
Endometrial cancer is a disease in which cancer cells form in the tissues of the inner lining of the uterus ( endometrium ).
Endometrial cancer is the most common cancer of the female genital tract.
Obesity, metabolic syndrome, and certain estrogen promoting medications may increase the risk of endometrial cancer.
Symptoms may include unusual vaginal bleeding or pain in the pelvis.
Lenvima was initially approved by the FDA in 2015 and Keytruda was initially approved in 2014.
The approval of Lenvima in combination with Keytruda id based on the results of a clinical trial of 94 patients with endometrial carcinoma tumors that were not MSI-H or dMMR.
Of the 94 patients, 10 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%, leading to an objective response rate of 38.3%.
Of these, 25 patients ( 69% of responders ) have a duration of response of greater than 6 months.
Common side effects for patients in the clinical trial 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.
Health care professionals should inform females of reproductive age and males with a female partner of reproductive potential to use effective contraception during treatment with Lenvima in combination with Keytruda.
Women who are pregnant or breastfeeding should not take this combination because it may cause harm to a developing fetus or newborn baby. ( Xagena )
Source: FDA, 2019