The first patient participating in the combination phase I/II study of MRx0518 and *KEYTRUDA® in collaboration with Merck & Co., Inc., Kenilworth, NJ., USA and 4D’s strategic collaboration with MD Anderson has completed Cycle 1 of Part A of the study with no dose limiting toxicities.
This study is open-label and will recruit up to 132 patients with metastatic cancer across multiple cancer types (non-small cell lung cancer, renal cell carcinoma, bladder cancer and melanoma) who have failed prior anti-PD-1 therapy. Part A of the study will enrol 12 patients with the primary outcome measure to assess safety and tolerability. Patients will continue on therapy with follow-up assessments including the anti-tumour effect of the combination. Recruitment is progressing as expected and we anticipate completing Part A before the end of 2019. At this point, Part B of the study, which has a primary endpoint to assess the clinical benefit of the combination, will commence.
Commencement of Phase I MRx0518 neoadjuvant monotherapy
In addition, phase I study of MRx0518 in a neoadjuvant setting has commenced. This placebo-controlled, phase I study at Imperial College London will evaluate MRx0518 as a monotherapy neoadjuvant in up to 120 treatment-naïve patients with solid tumours (melanoma, prostate, breast, ovarian, urothelial/bladder, renal, lung and head and neck cancers) who are due to undergo surgery as their first treatment. The primary endpoints of this study are safety and tolerability with secondary endpoints including tumour response, survival, immunological biomarkers and microbiome profiles. The principal investigator for this study is Dr. Jonathan Krell.
This study builds on the recently published data on the mechanism of action of MRx0518 that identified the bacterial flagellin (a specific component of the bacterium) as a potent stimulant of the innate and adaptive immune systems that interacts with the host TLR5 pathway known to be associated with the body’s response to cancer. Oncology is a core area of development at 4D and the focus on expanding clinical programmes in this space demonstrates 4D’s commitment to this disease area.
In addition to the monotherapy study, the combination phase I/II study of MRx0518 and Keytruda® in collaboration with Merck & Co., Inc., Kenilworth, NJ., USA, for patients who have relapsed or are refractory to PD-1 inhibitors is progressing as expected. Oncology is a core area of development at 4D and the focus on expanding clinical programmes in this space demonstrates 4D’s commitment to this disease area.
Duncan Peyton, 4D’s Chief Executive Officer, commented:
“We are delighted with the clinical progress of our oncology programme. The first patient completing Cycle 1 with no dose limiting toxicities gives us confidence that we may be able to report on early results of this study this year. The commencement of the monotherapy study significantly strengthens our understanding of the potential of MRx0518 to impact treatment across a range of cancer settings. The novel study design will, for the first time, enable the evaluation of the anti-tumour immunological effects of a Live Biotherapeutic in treatment-naïve patients who will not be receiving concurrent therapy. We see our continued research and focus on the mechanism of action of our Live Biotherapeutic products as crucial to their further clinical development and regulatory approval as we build our oncology franchise.”