I'd imagine they may already have a few patients lined up, but potentially even more after next week's presentation. Given the abysmal survival rates for Bile Tract cancer and completely inadequate therapy options, even though it's considered rare, I don't imagine it will take that long to enrol the ten patients.
To provide some shape around the current standard of care for unresectable biliary tract cancer which is gemcitabine combined with cisplatin (chemo combo) I have provided some data below:
Median OS ranges from 4.6 months (reported as 20 weeks) to 11.7 months and overall response rates ranged from 17.1% to 36.6%: based on 15 studies relating to this line of therapy . The included studies were conducted in a broad range of countries from North America, Europe, Australia, Asia, and Africa (Table 1). Most studies included participants with Eastern Cooperative Oncology Group performance status of 0 or 1, and with primary tumors from various sites. Sample sizes ranged from 10 [21] to 410 [17] participants; 912 participants received gemcitabine-cisplatin.
Out of a total of 912 patients (across the 15 studies), 17 achieved a CR, or 1.8%. Most of the 'Overall response rate' I quote above is attributable to partial responses. The durability of these responses is also very poor (relative to being cured), as highlighted by the Median OS at best being 11.7 months.
A more recent study (found here), one that also combined the MAB Durvalumab to gemcitabine with cisplatin, had better results.
Key points below:
685 patients were treated from April 2019. Data cut-off was in August 2021, so just over two years
At the data cutoff, 424 patients had died (62%)
Median overall survival was 12.8 months (95% CI, 11.1 to 14.0) in the durvalumab group
The number of patients achieving a confirmed complete response was 7 (2.1%) with durvalumab and 2 (0.6%) with placebo.
The number of patients achieving a confirmed partial response was 84 (24.6%) with durvalumab and 62 (18.1%) with placebo.
The percentage of patients with continued response for 12 months or more was 26.1% with durvalumab and 15.0% with placebo.
Grade 3 or 4 adverse events occurred in 256 patients (75.7%) in the durvalumab group and 266 patients (77.8%) in the placebo group (Table 3)
The table below is for anyone interested in the finer details.
The above sheds light on the best treatment outcomes from SOC/first-line therapy for unresectable bile tract (there is also some gall bladder for the review study) cancer. Our expansion trial will be in patients who have progressed off of the above therapy and likely a second-line therapy (FOLFOX/FOLFIRINOX etc), which is also a chemo combo.
So far, CF33 has been administered to only 2 patients with Bile Duct cancer, who both progressed through multiple lines of therapy (likely the ones above) and have both achieved a meaningful response in IT and IV. Anyone scoffing at these results has little to no understanding of how hard Bile Duct cancer is to treat and how significant the CR and SD is in this setting.
The question is, can CF33 build on these results and get an early win with this patient population? That's what we'll likely find out conclusively early next year. Although there are plenty more factors to consider, but anything better than the above would be significant and bode we'll for a confirmatory study to be granted. A few CRs and PRs in this cohort then happy days.
Frankly, we are now at the pointy end of the MAST trial, the data building from the recent cohorts and subsequent ones will be the most relevant and telling data. The data thus far while interesting shouldn't be extrapolated to draw any meaningful conclusions. It's a clinical trial, inherently they are learning and understanding daily what is happening and in reality only a few have been dosed at these meaningful doses, but still far from enough to draw any conclusions.
(20min delay)