Scandion Oncology has announced promising updated interim data from its Phase II CORIST trial, evaluating SCO-101 in patients with metastatic colorectal cancer (mCRC). The data, derived from Part 3 of the trial, confirms the rationale for the optimized dosing schedule of SCO-101 in combination with FOLFIRI, demonstrating encouraging pharmacokinetic data, biomarker potential, and early signs of efficacy, including overall survival (OS) benefits.
The CORIST trial is designed to assess the ability of SCO-101, Scandion Oncology's lead compound, to revert drug resistance in cancer cells. The updated data highlights early efficacy signals, including prolonged Progression-Free Survival (PFS), Clinical Benefit Rate, and partial tumor responses observed in two patients. Notably, a low Bilirubin Index (BI) was associated with increased PFS and improved OS, with 6 out of 9 patients in the low BI group remaining alive.
Further analysis revealed that patients with the UGT1A1 wildtype experienced significantly longer PFS and OS compared to those with mutated UGT1A1. Specifically, in UGT1A1 wildtype patients, the median PFS (mPFS) reached 7.04 months, and the median OS (mOS) was 13.74 months. These interim results are considered promising, with final data expected in the second half of 2024.
Optimized Dosing and Pharmacokinetics
The optimized dosing schedules led to anticipated changes in pharmacokinetics (PK). Data indicated a slight decrease (approximately 20%) in the maximum peak value (Cmax) of the active chemotherapy metabolite (SN-38) and an increase in the maximum peak value of SCO-101. Overall exposure to SN-38 and SCO-101 remained largely unchanged compared to Part 1 of the CORIST trial. Additionally, SCO-101 induced a clear increase in plasma levels of SN-38, causing a five-fold shift in the ratio between active and inactive SN-38, along with an increase in unconjugated bilirubin. This aligns with PK data from CORIST Part 1.
Management Perspectives
"These encouraging results confirm the rationale behind our optimized dosing strategy and highlight the significant potential of SCO-101 and our innovative mechanism of action to enhance treatment outcomes in this challenging patient population," stated Francois Martelet, CEO of Scandion Oncology. "Our next step is to expand the Part 3 data by adding one or more smaller patient cohorts to potentially further optimize the dosing regimen to be applied in a randomized trial."
Lars Damstrup, CMO at Scandion Oncology, added, "Altogether, the updated Part 3 interim data is very positive. Based on the current, still preliminary, overall survival data and based on data from Part 2 of the trial, we have data to support that these early signs of efficacy have the potential to translate into clinical meaningful improvement in overall survival, especially for the patients with positive biomarkers. Importantly, OS is the gold standard in oncology trials and an important regulatory endpoint – and is likely to be the primary endpoint in a future randomized Phase IIb clinical study."
Future Plans
Scandion Oncology intends to further explore the updated data by increasing the irinotecan component of FOLFIRI in a 4-day schedule with 250 mg of SCO-101. This aims to establish the Maximum Tolerated Dose (MTD) and define the Recommended Phase 2 Dose (RP2D) for the subsequent randomized Phase IIb study.
The topline data for mPFS, initially reported as 4.6 months including censored patients, was revised to a final value of 3.8 months for the 21 evaluable patients after uncensoring the data.
