Research from the Centre of Cancer Immunology which spans more than a decade has informed two new clinical trials investigating the potential of novel monoclonal antibodies to treat solid tumours, such as breast cancer.
In a pre-clinical study led by Professor Mark Cragg alongside Dr Ali Roghanian from the University of Southampton and Professor Bjorn Frendéus from BioInvent International an antibody called BI-1206, shown to target an immune receptor called FcgRIIB, and which overcame resistance of certain blood cancer cells to treatment. BI-1206 recruited immune cells toward the tumour and blocked the detrimental impacts of FcgRIIB. This enhanced an anti-cancer effect of other therapeutic antibodies, such as rituximab, by stopping them being absorbed by the tumour cells.
Following this successful lab-based research, a study led by Professor Andrew Davies at the University of Southampton went on to conduct first in human trials of BI-1206, funded by Blood Cancer UK and BioInvent International and sponsored by CRUK, to assess the maximum dose that could be given safely to humans alone and in combination with rituximab.
Ongoing clinical studies conducted by BioInvent International evaluate BI-1206 in combination with rituximab for the treatment of Non-Hodgkin’s Lymphoma, which includes patients with Follicular lymphoma, Mantle Zone Lymphoma and Marginal Zone Lymphoma who have relapsed or are refractory to rituximab*.
More recently, the team demonstrated that targeting the inhibitory FcgRIIB can potentiate immunotherapy of solid tumours.
This body of research is now supporting two new trials, which have begun recruiting patients.
The first trial will assess the ability of BI-1206 to reverse an important mechanism of resistance to the so-called immune checkpoint blocker, pembrolizumab, providing a way to enhance anti-tumour immune responses in patients with solid tumours**.
The second trial, which recently received FDA IND approval***, will investigate the combination of another FcgRIIB antibody (BI-1607) in combination with trastuzumab, which is used to treat breast cancer patients.
Similar to BI-1206, BI-1607 is intended to enhance the efficacy and overcome resistance to existing cancer treatments such as trastuzumab****. The ongoing first-in-human Phase 1 trial is a dose escalation study of BI-1607 combined with trastuzumab in HER2+ advanced or metastatic solid tumours.
Professor Mark Cragg said: “Southampton has a rich history of taking lab-based research into the clinic and this demonstrates our commitment to help treat cancer patients. We are very proud that our original research, undertaken alongside BioInvent International, is progressing through additional clinical studies with the possibility of making positive impacts on patients’ lives.”
References
*https://www.bioinvent.com/en/clinical-programs/our-programs/bi-1206rituximab
**https://www.bioinvent.com/en/clinical-programs/our-programs/bi-1206pembrolizumab
****https://www.bioinvent.com/en/clinical-programs/our-programs/bi-1607