The company has announced data from part 2 of its international multi-center CORIST open label phase IIa trial.
The 25 enrolled patients in CORIST part 2 were heavily pretreated and no other active treatment options were available. The data documents long survival for wild type KRAS patients with metastatic colorectal cancer (mCRC) participating in the trial, states the company.
This new data adds to the topline results from CORIST part 2 announced in September 2022 which confirmed the safety and tolerability of SCO-101 in combination with chemotherapy FOLFIRI in patients with metastatic colorectal cancer.
“We are encouraged by these promising overall survival data for this hard-to-treat refractory patient population. Ultimately, prolonged overall survival is the most important outcome of any cancer treatment. This is promising data for the continued development of SCO-101 and the ongoing part 3 of CORIST,” says Lars Damstrup, Chief Medical Officer of Scandion.
CORIST Part 2
In CORIST part 2, OS was evaluated as a secondary endpoint. Median OS in the 25 patients was 10.4 months while historical data for placebo or best supportive care have been reported in the range of 5-7 months in large international, multicenter, randomized, double-blinded phase III trials. Of note, seven of the 25 patients participating in part 2 of the trial are still alive more than 15 months after start of treatment, describes the company. This clinically meaningful improvement in mOS is important as OS is the gold standard in oncology trials and an important regulatory endpoint, describes the company.
Another secondary endpoint in the trial was Progression Free Survival (PFS) and the median was 2.0 months with historical data having been reported in the range of 1.7-1.8 months.
The Clinical Benefit Rate (CBR), which was assessed after 16 weeks as defined in the protocol, was found to be 21%. Historical controls where CBR was evaluated after 6 weeks have been reported to be 11-16%. Whereas the CBR after 8 weeks in CORIST part 2 was found to be 42%. This may be further evidence of positive efficacy data from CORIST part 2, states the company.
Further, tumor shrinkage was observed in four patients (out of 25 patients), however that is below the +30% threshold defined as the trial’s primary endpoint. “It is encouraging to see tumor reductions in four patients, a high proportion in this group of refractory hard-to-treat patients,” states the company.
Potential biomarker identified
Another secondary endpoint of CORIST part 2 was to evaluate clinical biomarkers, which was achieved as unconjugated bilirubin was identified as a potential blood-based biomarker for patients most likely to respond to SCO-101. In the trial it was observed that 17 out of 25 patients had a transient increase in unconjugated bilirubin whereas the other eight patients had a more persistent increase. Separating the patients into “transient” and “persistent” bilirubin responses shows clear differences in median OS and PFS. Comparing OS, the “transient” group had a significantly higher median of 13.4 months vs. 8.0 months in the “persistent” group (P=0.0011). The “transient” group had a non-significant increase in median PFS of 2.0 months vs. 1.8 months in the “persistent” group (P=0.1361). Notably, the seven patients (7/17=41%) from CORIST part 2 still alive are all in the “transient” group and therefore the survival for these patients will further improve, describes the company.
“The separation of a transient and persistent group with respect to unconjugated bilirubin is in line with data from both part 1 of CORIST8 and from our phase I clinical trials in healthy volunteers, where SCO-101 was administered as a single drug,” states the company. “Importantly, the assay to measure and quantify bilirubin in the blood is a worldwide standardized assay, routinely conducted at hospitals. This should allow for easy application of the bilirubin as a potential biomarker to identify patients that will have the greatest benefit for SCO-101 treatment.”
“Furthermore, the overall survival in the subset of patients with transient high levels of unconjugated bilirubin is rather impressive. We are aware of the small number of patients, however, implementing a ready to use potential biomarker would have a great impact in potentially predicting the clinical outcome for these patients with mCRC. This hypothesis needs to be evaluated in a prospective randomized clinical trial,” concludes Lars Damstrup.
Photo of Lars Damstrup: Scandion Oncology
