November 22, 2023

Kristi Rosa

SCO-101 in combination with leucovorin, fluorouracil, and irinotecan (FOLFIRI) provided a clinically meaningful overall survival benefit in heavily pretreated patients with metastatic colorectal cancer who had no other active treatment options available, according to final data from part 2 of the phase 2 CORIST study.

Colorectal Cancer

Colorectal Cancer

SCO-101 in combination with leucovorin, fluorouracil, and irinotecan (FOLFIRI) provided a clinically meaningful overall survival (OS) benefit in heavily pretreated patients with metastatic colorectal cancer (mCRC) who had no other active treatment options available, according to final data from part 2 of the phase 2 CORIST study (NCT04247256).1

In 25 evaluable patients, the median OS was 10.4 months, with 7 patients still alive 15 months after treatment initiation. Historical data from international, multicenter, randomized, double-blinded, phase 3 trials have demonstrated a median OS ranging from 5 to 7 months with placebo or best supportive care (BSC), according to Scandion Oncology.

Moreover, the median progression-free survival (PFS) experienced with the regimen was 2.0 months. Historical data have showcased a median PFS ranging from 1.7 to 1.8 months. After 16 weeks, the clinical benefit rate (CBR) was reportedly 21% with the SCO-101 regimen; after 8 weeks, the CBR was 42%. Historical controls have had CBRs ranging from 11% to 16% after 6 weeks.

“We are encouraged by these promising OS data for this hard-to-treat refractory patient population. Ultimately, prolonged OS is the most important outcome of any cancer treatment,” Lars Damstrup, chief medical officer of Scandion Oncology, stated in a press release. “This is promising data for the continued development of SCO-101 and the ongoing part 3 of CORIST.”

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

CORIST is comprised of 3 parts. In part 1, the dose-escalation phase, investigators sought to identify the maximum-tolerated dose of SCO-101 plus FOLFIRI.3 This was successfully completed in June 2021. Patients received the investigative agent once daily on days 1 to 6 and FOLFIRI was given on days 5 to 7.

Based on findings from the first portion, part 2 only included patients with RAS wild-type tumors (n = 25) and they received SCO-101 and FOLFIRI over the course of 7 days. The key objectives of this part of the research focused on efficacy.

In September 2022, topline results from part 2 of CORIST were released and showed that SCO-101 plus FOLFIRI given in a schedule of over 7 days was feasible, safe, and tolerable.4,5 Four out of the 25 evaluable patients experienced a reduction in tumor burden; however, that was noted to be below the +30% threshold that represented the trial’s primary end point. Because no responses were observed at the planned timepoint of 8 weeks from treatment initiation, proof of concept for efficacy was not reached. It was concluded that the findings still supported study expansion.

Additional data from the final report of part 2 revealed that unconjugated bilirubin could represent a blood-based biomarker for those who have increased likelihood to respond to SCO-101.1 Specifically, 17 out of the evaluable patients were noted to have a transient increase in this marker and the other 8 patients had a persistent increase.

Those in the transient subset experienced a significantly higher median OS than those in the persistent subset, at 13.4 months and 8.0 months, respectively (P = .0011). The median PFS in the transient subset was 2.0 months vs 1.8 months in the persistent subset, a difference that was not determined to be significant (P = .1361). Forty-one percent of those in the transient subset were still alive at the time of the report.

“…The OS in the subset of patients with transient high levels of unconjugated bilirubin is rather impressive,” Damstrup added in the press release. “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.”

Scandion Oncology received approvals from authorities and ethical committees in Denmark and Germany to proceed with the next parts of the trial in August 2022.6 In the third quarter of 2022, recruitment was initiated for part 3.4 A new schedule for the regimen given over 6 days will be examined in up to 36 patients with RAS wild-type and RAS-mutated mCRC in up to 6 escalation cohorts.5 The key objectives are to assess safety and efficacy in this population.

References

  1. Final data from the phase IIA open-label CORISE part 2 trial shows impressive median overall survival of 10.4 months. News release. Scandion Oncology. November 21, 2023. Accessed November 21, 2023. 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/

  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 November 21, 2023. https://clinicaltrials.gov/study/NCT04247256

  3. Clinical development: SCO-101 combined with FOLFIRI in metastatic colorectal cancer. Scandion Oncology website. Accessed November 21, 2023. https://scandiononcology.com/research-development/clinical-development/#corist-phase-ii

  4. Scandion Oncology announce topline results from part 2 of the CORIST phase II trial. News release. Scandion Oncology. September 30, 2022. Accessed November 21, 2023. https://scandiononcology.com/2022/09/scandion-oncology-announce-topline-results-from-part-2-of-the-corist-phase-ii-trial/

  5. CORIST topline results: webcast. Scandion Oncology. October 4, 2022. Accessed November 21, 2023. https://scandiononcology.com/wp-content/uploads/2022/10/221004-CORIST-topline-investor-presentation.pdf