This mogamulizumab anti-CCR4 monoclonal antibody is extremely important because it is the first, if approved, indication in the US for any condition. We’re very excited that the MAVORIC study has concluded giving very positive results that have been submitted to the FDA. I got delayed coming here because the FDA just audited the lead centre and it was very well done and the results are outstanding and very validated by the FDA, at least at our centre.
I would like to make sure that I credit the international community and all of the family and patients that have participated in this study up front. I represent all of them.
The target for this mogamulizumab is C-C chemokine receptor 4, CCR4, and it plays a very important immune balance role in life. It’s expressed in Th2 and Treg cells and it is involved in trafficking of T lymphocytes actually to the skin and other organs. It is also highly over-expressed, and consistently so, in ATL, PTCL and cutaneous T-cell lymphoma and thus the subject of this antibody. Mogamulizumab is FC bioengineered enhanced, it removes the fucose, defucosylated antibody that augments the antibody dependent cell cytotoxicity which is a mechanism of this antibody.
It was based on the phase I/II study in CTCL that was already conducted in the US with a very promising efficacy profile. 37% overall response and in this disease it is a very good response rate because all the FDA approved drugs are in the 30% range. Also 95% response in the blood, so the blood compartment appears to have good response. Encouraging results led to the phase III randomised controlled trial, MAVORIC, which was completed and subject of this presentation. The primary endpoint is progression free survival. It is the largest study ever in CTCL to be randomised and have PFS as an endpoint.
The eligibility was stage 1b-4 with confirmed diagnosis and you have to have had at least one prior therapy. Patients with large cell transformation were excluded. Patients were randomised one to one to mogamulizumab and to vorinostat; mogamulizumab was given 1mg/kg IV. It’s given weekly in the first month, then it goes to every two weeks thereafter. Both arms were treated until disease progression or if the vorinostat group has intolerable toxicity or progresses there is a one-way crossover to get the active drug, mogamulizumab. Patients in the vorinostat were treated accordingly to the US prescribed guidelines. It is an approved drug in the US for this CTCL. CCR4 expression level was not required for eligibility for this study and about sixty centres across eleven countries were involved in the study. The primary endpoint, as I mentioned, is PFS. Using a very vigorous comprehensive composite global you have to group all of the compartments together to have a response. The key secondary endpoints are duration of response and patient reported quality of life as well as the crossover response and safety. There were independent review groups that reviewed the investigator data.
The two arms, mogamulizumab and vorinostat were very well balanced. In total 372, 186 each, were enrolled and, as I said, this is the largest US study for this orphan disease. It took over three years to enrol. The two groups were very well balanced in terms of stage, MF versus Sézary syndrome, and the median prior therapy was three systemic treatments.
This is the primary endpoint which was 7.7 months in the mogamulizumab and 3.1 months in the vorinostat with a strikingly impressive superior result in mogamulizumab with a p-value of 0.0001. Also, the overall response rate in the mogamuzlizumab was about 30% with vorinostat only 5%. In the Sézary syndrome the response rate is higher, as expected, 37% over vorinostat of only 2%. These are confirmed global composite response of all the compartments – skin, lymph node, blood, viscera – they’re all integrated into this response criteria so it’s not just skin response. Duration of response, as expected, greater in mogamulizumab and the quality of life was much better in the mogamulizumab arm.
In summary, this is the first report of a randomised phase III study evaluating the PFS as a primary endpoint in CTCL to compare a new systemic therapy against an FDA approved agent utilising a consensus comprehensive global response criteria. Mogamulizumab, a novel CCR4 targeting antibody therapy, demonstrated significantly superior efficacy outcomes compared to vorinostat in patients with previously treated CTCL. The PFS, 7.7 months versus 3.0 months was p-value of 0.001 significance. Overall response was again highly superior with a similar striking significance of 28% versus 5%. Patient reported outcome using the tools that are used, Skindex-29 fac-2 were demonstrating a significant improvement in the mogamulizumab arm and overall safety profile, there were no surprises in the mogamulizumab. It is approved in Japan for ATL, PTCL and CTCL in Japan, thus it has been used there and there was no new surprising AE profile that was detected in this randomised trial and vorinostat was as well. Any side effect was very manageable.
The study supports mogamulizumab as a valuable new therapeutic option in the patients with CTCL and we’re very excited and we hope that this drug will be approved early next year to add to the limited options that we have in our patient population. Thank you.