SCO-101 Plus FOLFIRI Will Continue to Be Studied Despite Missing Primary End Point in mCRC

The addition of SCO-101 to FOLFIRI chemotherapy was safe and tolerable but failed to elicit a greater than 30% reduction in tumor volume in patients with metastatic colorectal cancer, though study of the combination will continue.

The addition of SCO-101 to FOLFIRI chemotherapy was safe and tolerable but failed to elicit a greater than 30% reduction in tumor volume in patients with metastatic colorectal cancer (mCRC), failing to meet the primary end point of part 2 of the phase 2 CORIST trial (NCT04247256).1,2

Improvements in progression-free survival (PFS) and rates of stable disease—key secondary end points of the trial—were also shown. The data were collected from 25 patients enrolled in part 2, most of whom had been evaluated after only 8 weeks of treatment.

“While we do not achieve a clinical proof of concept for efficacy through these topline results, we are encouraged by the signals observed in the trial, confirming the rationale for combining SCO-101 and FOLFIRI in this indication. We look forward to continuing the development by progressing the CORIST trial further as planned,” Johnny Stilou, acting chief executive officer of Scandion, said in a press release.

SCO-101 is an ABC efflux pumps and SRPK1 kinase inhibitor, which plays a key role in phosphorylation of splicing factors and tumor growth.

The addition of SCO-101 to FOLFIRI is thought to inhibit the active efflux of chemotherapy molecules from the cancer cell, re-sensitizing it to chemotherapeutic agents.

CORIST is a multi-center, open-label, dose-escalation, phase 2 study evaluating SCO-101 plus FOLFIRI in up to 50 patients with mCRC with acquired resistance to prior FOLFIRI.

To be eligible for enrollment, patients must be at least 18 years old with histologically confirmed colorectal adenocarcinoma, a maximum tumor reduction of 33% with prior FOLFIRI, a performance status of 0 or 1, and life expectancy of at least 3 months.

In the study, patients will receive FOLFIRI on days 5 to 7 plus SCO-101 as an oral tablet on day 1 to 6. Treatment will be administered every 14 days.

The primary end points of the study are objective response rate, incidence of treatment-emergent adverse effects, and maximum-tolerated dose. Key secondary end points include PFS, duration of response, overall survival, and clinical benefit rate.

Per the press release, the study will continue as planned and will enroll up to 36 patients to receive an optimized dosing schedule in part 3 of the trial. Increased doses of SCO-101 and FOLFIRI will be evaluated based on an improved understanding of the pharmacokinetics of the agent in combination with chemotherapy. The first patient is expected to enroll in part 3 soon.

Notably, part 3 of the study may conclude by the third quarter of 2023 based on the dose-escalation results. An update on the timeline is expected in the first quarter of 2023, which will include the timeline for part 4 of the trial, which will conclude the study.

References

  1. Scandion Oncology announce topline results from part 2 of the CORIST phase II trial. News release. Scandion Oncology. September 30, 2022. Accessed October 4, 2022. https://bit.ly/3e2ZeSS
  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 October 4, 2022. https://clinicaltrials.gov/ct2/show/NCT04247256