FDA approved Cotellic tablets (cobimetinib) for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib. Cobimetinib is not indicated for treatment of patients with wild-type BRAF melanoma.
The approval was based on the demonstration of improved progression-free survival and overall survival in a double-blind, randomized, active-controlled trial conducted in 495 patients with previously untreated, BRAF V600 mutation-positive, unresectable or metastatic melanoma as detected using the cobas 4800 BRAF V600 mutation test. Cobimetinib is sponsored by Genentech.
All patients received vemurafenib 960 mg orally twice daily and were randomized (1:1) to receive cobimetinib 60 mg (n=247) or matching placebo (n=248) orally once daily on days 1-21 of an every 28-day cycle. The median age of the study population was 55 years (range 23 to 88 years), 60 percent had stage M1c disease, 72 percent had a baseline ECOG performance status of 0, 45 percent had an elevated baseline serum lactate dehydrogenase, 10 percent had received prior adjuvant therapy, and less than 1 percent had previously treated brain metastases.
The trial demonstrated a statistically significant improvement in PFS [HR: 0.56 (95% CI: 0.45, 0.70), p < 0.001]; the median PFS was 12.3 months (95% CI: 9.5, 13.4) and 7.2 months (95% CI: 5.6, 7.5) on the cobimetinib plus vemurafenib and single-agent vemurafenib arms, respectively.
The trial also demonstrated a statistically significant improvement in OS based on an interim analysis [HR: 0.63 (95% CI: 0.47, 0.85); stratified log-rank p-value=0.0019]. The median OS was not reached (95% CI: 20.7, NR) and was 17 months (95% CI: 15.0, NR) on the cobimetinib plus vemurafenib and single-agent vemurafenib arms, respectively.
The confirmed objective response rates were 70 percent (95% CI: 64, 75) and 50 percent (95% CI: 44, 56) on the cobimetinib plus vemurafenib and single-agent vemurafenib arms, respectively (p < 0.001).
Safety data was evaluated in 247 patients who received at least one dose of cobimetinib. The most common adverse reactions were diarrhea, photosensitivity reaction, nausea, pyrexia, and vomiting. The most serious risks in patients receiving cobimetinib were new primary malignancies, hemorrhage, cardiomyopathy, severe dermatologic reactions, serous retinopathy and retinal vein occlusion, hepatotoxicity, rhabdomyolysis, and severe photosensitivity reactions.
The University of Chicago and Evelo Therapeutics will collaborate on an immunotherapy that employs certain gut microbes to boost the immune system’s attack on cancer cells and improve the effectiveness of anti-cancer drugs.
An exclusive agreement between the University of Chicago and Evelo provides the company with the option to acquire worldwide rights to the microbiome-based immunotherapy.
In a study published in Science, University of Chicago researcher Thomas Gajewski showed that certain species of bacteria added to the digestive tracts of mice increased the ability of the animals’ immune systems to attack tumor cells and, when combined with anti-PD-L1, an investigational anti-cancer antibody in the drug class known as checkpoint inhibitors, nearly eradicated tumors.
