The work that I presented at ASCO this year was the FIGHT randomised phase II study. This was a study for gastroesophageal adenocarcinoma that was either overexpressing FGFR2b by immunohistochemistry or showing circulating tumour DNA positivity for gene amplification, so either/or. The study was previously reported for the primary endpoint of the intention to treat analysis of progression free survival at GU ASCO this year. What we presented at this meeting was updated information in terms of subgroup analyses, demographics like gender, age, sex and whether or not patients had a dose of FOLFOX chemotherapy or not during screening as well as the molecular subgroups in terms of those patients who had ctDNA positivity and their outcomes and those patients who had IHC positivity only, for example, and their outcomes.
Then we presented the median overall survival which previously had not been reached at the first data cut. With the new data cut more recently showing the median overall survival by the intention to treat analysis and then also by pre-specified secondary analyses of expression level by 5% of tumour cells or higher or 10% of tumour cells or higher. Then finally we updated some information about the corneal toxicity AEs that were noted and some of the other nuances about that.
So, overall what we showed was that by subgroups and all of the subgroup characteristics and molecular profiles that there was a benefit across the groups. There was more profound benefit in the ctDNA positive tumours, as might be expected, but in even in patients that had tumours that were IHC positive but ctDNA negative still demonstrated improved PFS and OS with a hazard ratio of 0.66. In contrast, the ctDNA positive tumours had a hazard ratio of 0.1.
Then the big news was the overall survival which again had not been reached previously. Now in the intention to treat analysis it was 19.5 months in the bemarituzumab arm compared to 11 months in the placebo controlled arm. In the 5% or higher cut-off of expression it still had not been reached which was upwards of 75% of all the patients. 10% or higher cut-off, which was about 62% of all the patients, the median overall survival estimate was around 25 months. So quite outstanding survival in a randomised placebo controlled global study.
Then the corneal toxicities we noted that any grade corneal toxicity occurred in about 67% of patients and it was evenly split 20%-20%-20% approximately for grade 1, 2 and 3. Then we also presented the median time to onset of grade 2 or higher corneal toxicity which was around 24 weeks and the median time to resolution to at least grade 1 or lower corneal toxicity was also around 19 weeks. So the significance of that is that with that long lead time in terms of developing a grade 2 toxicity that there may be possibilities to mitigate that with some prophylactic measures which were not done in this study but certainly will be assessed in future trials.
The next steps for this programme, then, are first of all the publication of this is in the works to really get down to all the details and to really show the efficacy and highlight that in terms of an improved progression free survival as the primary endpoint, response rate increase of 13% in all comers and then increased by the higher threshold cut-offs of the biomarker – 18% higher response rate in the 10% threshold of expression. Then the median overall survivals which are outstanding.
Secondly, prospective studies in the first line setting, a randomised phase III study is planned to confirm what we’ve seen here in this randomised phase II study. So we look forward to that in the very near future.
One other thing to add now in this ever-changing and rapidly changing landscape of first line therapy for gastroesophageal adenocarcinoma is that not that long ago when the standard of care for all comers was chemotherapy and then we were introduced to HER2 positivity for about 10-15% of patients. Today we have a number of candidate biomarkers with very promising efficacy endpoints including bemarituzumab for FGFR2 positive tumours and others as well including claudin potentially which has phase III studies and of course now with immunotherapy checkpoint inhibitors, certainly for PD-L1 high tumours and MSI high tumours. So we have choices now and it’s going to be really paramount for us to prioritise therapies for our patients to give each patient their best choice based on their biology and their cancer and I think that it’s very exciting times that we have this choice.
The other point is to say that future studies will now be looking at potential combinations of these various targets for these various subgroups.