SCO-101 Plus FOLFIRI Shows Signs of Efficacy in Metastatic Colorectal Cancer

The combination of SCO-101 and leucovorin, fluorouracil, and irinotecan (FOLFIRI) resulted in tumor reduction and increased progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), according to data from a preliminary analysis of part 3 of the phase 2 CORIST study (NCT04247256).¹

A total of 25 patients with mCRC who were heavily pretreated, showed prior evidence of resistance to FOLFIRI, and who have no active therapeutic options available to them were enrolled to part 3 of the study. The maximum tolerated dose (MTD) was established at 150 mg given as part of a 6-day schedule. The combination was found to be safe and tolerable.

In one of the cohorts that used a 4-day dosing schedule, 6 patients achieved partial responses defined as tumor reduction of greater than 30%. In the total population of 21 evaluable patients divided into 4 cohorts, “a substantial number of patients” experienced tumor reductions, according to a press release issued by Scandion Oncology.

The overall median PFS experienced with the combination was 4.6 months. In one of the cohorts in part 3, the median PFS was 5.0 months. In a cohort of patients where the MTD dose had been determined, the clinical benefit rate (CBR) achieved with the regimen at week 8 was 76%; after 8 weeks, the CBR was 100%.

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

The multicenter, open-label, prospective phase 2 study included patients with histologically verified colorectal adenocarcinoma who were at least 18 years of age, who achieved a maximum tumor reduction of 33% with prior FOLFIRI, had a performance status ranging from 0 to 1, and had a life expectancy of at least 3 months.²

SCO-101 inhibits the drug efflux pump and cancer stem-cell marker ABCG2.³ Investigators hypothesized that pairing this investigative drug with chemotherapy would boost the intracellular concentration of the chemotherapy and result in more cancer cell death. The agent also inhibits UGT1A1, a liver enzyme that metabolizes several approved drug substrates, including SN-28.

The study was comprised of 3 parts. In the dose-escalation phase, or part 1, investigators set out to determine the MTD of SCO-101 paired with FOLFIRI.⁴ This was successfully completed in June 2021. Patients received SCO-101 once daily on days 1 through 6 and FOLFIRI was administered on days 5 through 7.

Part 2 of the study only included patients with RAS wild-type tumors (n = 25), and they were given SCO-101 plus FOLFIRI over 7 days. The key objectives of this part of the research focused on efficacy.

In September 2022, topline data from this part of the research showed that when the combination was given in a schedule of 7 days, it was feasible, safe, and tolerable.^5,6 Of 25 evaluable patients, 4 achieved tumor burden reduction; this fell below the +30% threshold that represented the primary end point of the research. Moreover, no responses were observed at the planned time point of 8 weeks from treatment initiation, so proof of concept for efficacy was not reached. However, it was concluded that the data still supported study expansion.

Final data from part 2 were released in November 2023.7 In the 25 evaluable patients, the median overall survival, a secondary end point, was 10.4 months. Seven of the 25 patients were still alive more than 15 months after treatment had been initiated. Moreover, the median PFS was 2.0 months. After 16 weeks, the CBR was 21%; after 8 weeks, this rate had been 42%. Four patients experienced tumor reduction, but it was below the +30% threshold.

Scandion Oncology received approvals to move forward with the next parts of the trial in August 2022.⁴ The trial was expanded by adding a new schedule where the regimen was given over 6 and 4 days in patients with RAS wild-type and RAS-mutated tumors. Recruitment to part 3 began in the third quarter 2022.⁵

The company plans to conduct a “thorough analysis” of the data set from part 3 of the study after trial completion. Based on the preliminary analysis, they shared plans to move forward with the next steps in clinical development.

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 1, 2024. https://scandiononcology.com/mfn_news/scandion-oncology-reports-positive-topline-phase-iia-data-from-the-corist-part-3-trial/
2. A phase 2 trial of SCO-101 in combination with FOLFIRI for patients with metastatic colorectal cancer (mCRC) with acquired resistance to FOLFIRI. ClinicalTrials.gov. Updated March 2, 2022. Accessed February 1, 2024. https://clinicaltrials.gov/study/NCT04247256
3. SCO-101. Scandion Oncology website. Accessed February 1, 2024. https://scandiononcology.com/sco-101-2/
4. Clinical Development: SCO-101 combined with FOLFIRI in metastatic colorectal cancer. Scandion Oncology website. Accessed February 1, 2024. https://scandiononcology.com/research-development/clinical-development/
5. Scandion Oncology announce topline results from part 2 of the CORIST phase II trial. News release. Scandion Oncology. September 30, 2022. Accessed February 1, 2024. https://scandiononcology.com/2022/09/scandion-oncology-announce-topline-results-from-part-2-of-the-corist-phase-ii-trial/ 
6. CORIST topline results: webcast. Scandion Oncology. October 4, 2022. Accessed February 1, 2024. https://scandiononcology.com/wp-content/uploads/2022/10/221004-CORIST-topline-investor-presentation.pdf
7. Final data from the phase IIA open-label CORSIT part 2 trial shows impressive median overall survival of 10.4 months. News release. Scandion Oncology. November 21, 2023. Accessed February 1, 2024. https://scandiononcology.com/mfn_news/final-data-from-the-phase-iia-open-label-corist-part-2-trial-shows-impressive-median-overall-survival-of-10-4-months/