An update on a study of CytomX’s recently declared lead project, the masked anti-EpCAM ADC varsetatug masetecan – now including three times as many patients as in an earlier data cut – has shown a typical falling off in efficacy, with response rates standing at 20%, versus the 28% reported last year.
That said, the setting in question, late-line colorectal cancer, is tough, and CytomX will hope to have done enough to back advancing varseta-M into pivotal development. Importantly, even the reduced ORR numbers look better than comparators on a cross-trial basis, as does an update on progression-free survival, and toxicity fears might have been allayed.
The update, given on Monday, was a vital catalyst for CytomX investors, who had sent their company’s shares up nearly 700% over the past year in expectation, after the company pivoted to varseta-M as its pipeline lead. The stock closed up 44%, taking CytomX well above the $1bn market cap barrier.
26% response rate
The main reason behind the enthusiasm is that 8.6mg/kg and 10.0mg/kg, the two highest of the three varseta-M doses CytomX is testing in this trial, have delivered a 26% ORR now among 39 evaluable patients, plus estimated median PFS of 6.8 and 7.1 months respectively.
On a cross-trial basis this looks far in excess of competitor data in late-line colorectal cancer, where only Cabometyx and Lenvima – both combined with PD-(L)1 blockade – have managed ORRs in the double digits, and where mPFS runs at well under four months. CytomX was also testing 7.2mg/kg in dose expansion, but it’s now clear that this is insufficiently active, and won’t be taken forward.
On the debit side, this dataset last year was showing a 28% ORR across all three doses, with the two highest ones running at 31%. However, that involved only 18 patients in total and, as ApexOnco argued at the time, it would have been unrealistic to expect response rates to remain near 30% in a substantially larger population.
Much more important than this is varseta-M’s safety: last year’s revelation of high rates of grade 3 diarrhoea, plus a death due to kidney injury, saw CytomX shares punished. On Monday CytomX reported no additional deaths, and suggested that diarrhoea was being kept under control.
While 81% of dose-expansion patients experienced diarrhoea (29% at grade 3+), there was a different picture in dose-optimisation, which currently involves 20 patients at 8.6mg/kg and 10.0mg/kg alone, and mandates prophylaxis with anti-motility drugs and budesonide. Here the diarrhoea rate was still a high 95%, but grade 3+ diarrhoea was seen in only 10%.
How CytomX’s varseta-M dataset has evolved
| 7.2mg/kg | 8.6mg/kg | 10.0mg/kg | Total |
|---|
| 4 Jul 2025 cutoff | ORR | 20% (1/5) | 17% (1/6) | 43% (3/7) | 28% (5/18) |
| mPFS | NA | NA | NA | 5.8mth |
| 16 Jan 2026 cutoff | ORR | 6% (1/17) | 20% (4/20) | 32% (6/19) | 20% (11/56) |
| mPFS | 5.5mth | 6.8mth | 7.1mth | ~7mth |
CytomX’s hope is to bring varseta-M to market in a biomarker-unselected colorectal cancer population, based on its observation that this cancer features high levels of EpCAM expression.
Monday’s data backed this too: the study didn’t mandate expression of this biomarker, but of the 56 efficacy-evaluable patients 49 were found to have high EpCAM levels. Another two had EpCAM expression only a little lower, while tumour tissue for the remaining five wasn’t evaluable for the biomarker.
CytomX is continuing to pursue 8.6mg and 10.0mg in optimisation, but it’s next goal is to start a registrational trial, presumably testing just one selected varseta-M dose. For that to happen it needs to agree a trial design with the FDA; “interactions” with the agency over this are promised around the middle of the year.
