Novel Drug Shows Increased Efficacy in Small Metastatic CRC Population

Moving forward, investigators of the phase 2a CORIST trial (NCT04247256) plan to add 1 or more cohorts to the 4-day dosing schedule to increase efficacy but not toxicity. Additionally, they will explore if bilirubin can be used as a potential biomarker.

The use of SCO-101 plus leucovorin, fluorouracil, and irinotecan (FOLFIRI) was found to increase efficacy and maintain safety and tolerability for a small cohort of patients with metastatic colorectal cancer (CRC), according to results from part 3 of the phase 2a CORIST trial (NCT04247256).¹

In part 3, the median progression-free survival (PFS) was 4.6 months, and after 8 weeks of treatment, the clinical benefit rate (CBR) was 76%. The PFS in part 2 was 2.0 months, and the CBR was 46%.

“We are very encouraged by the promising topline results reported today, not only establishing a maximum tolerated dose for this indication and drug combination but also demonstrating impressive [PFS] for the participating patients and tumor shrinkage in a number of them. These results strongly support the potential of SCO-101 as a combination treatment of metastatic [CRC], a disease that is today characterized by high mortality rates and massive problems with addressing drug resistance. We look forward to the final analysis and to taking the next step with SCO-101,” Francois Martelet, chief executive officer at Scandion Oncology, said in the press release.

Additional results were presented during a live session.² A total of 25 patients were enrolled, with patients receiving SCO-101 at either 150 mg (n = 7), 200 mg (n = 11), or 250 mg (n = 7). The maximum tolerated dose (MTD) was established at 150 mg on a 6-day schedule and the multiple ascending dose (MAD) was established at 250 mg on a 4-day schedule. For the MTD, patients received SCO-101 on days 1 to 6. For the MAD, patients received SCO-101 on days 1 to 4. Follow-up is currently ongoing.

Patients were eligible to enroll if they had acquired resistance to FOLFIRI, were older than 18, had a maximum reduction of 33% prior to FOLFIRI, and had an ECOG performance status of 0 to 1. Patients were also enrolled if they had a life expectancy of 3 or more months.

Part 3 of this study was designed to determine the optimal activity of SCO-101 and its dosing schedule. Investigators designed a dose escalation for enrolled patients irrespective of a KRAS mutation. For dosing regimen 1, SCO-101 was given on days 1 to 6. Patients in cohort 1 received 150 mg (n = 4), cohort 2 was given 200 mg (n = 4), and cohort 3 was given 150 mg (n = 3). There were 2 dose-limiting toxicities experienced in 4 patients. In dosing regimen 2, SCO-101 was given on days 1 to 4, with patients in cohort 4 receiving 200 mg (n = 7), and cohort 5 receiving 250 mg (n = 7). There were no dose-limiting toxicities observed.

After the key findings were analyzed, 3 patients continued treatment. Looking at historical data, SCO-101 delayed progression by more than 2.8/2.9 months. Looking at the CBR, when evaluated after 6 weeks, historical control rates were reported to be between 11% and 16%.

Moving forward, investigators plan to add 1 or more cohorts to the 4-day dosing schedule to increase efficacy but not toxicity. Additionally, they will explore if bilirubin can be used as a potential biomarker.

“We need proof of concept. We will conduct a randomized phase 2 trial to maximize the efficacy of SCO-101. Additionally, we’d like to see an enabling study to optimize the 4-day dosing scheduling,” Lars Damstrup, MD, PhD, chief medical officer at Scandion Oncology, said in the live presentation.

References

1. Scandion Oncology reports positive topline phase IIA data from the CORIST part 3 trial. News release. Scandion Oncology. January 31, 2024. Accessed February 5, 2024. https://shorturl.at/qwZ24
2. Scandion Oncology R&D and investor day with Q&A. YouTube page. Accessed February 5, 2024. https://bit.ly/3uw8OG5