Extended efficacy and safety data
Safety extension cohort I and II (31 patients): Overall Response Rate after 16 weeks treatment with arfolitixorin
In September 2020, Isofol announced response assessment data from the two safety extension cohorts (31 patients) treated for 16 weeks or longer. The data showed a best overall response rate (ORR) of 55 %. These patients were treated with the selected dose regimen of 120 mg/m2 arfolitixorin and 5-fluorouracil (5-FU) with either irinotecan or oxaliplatin (ARFIRI/ARFOX). Out of the 31 patients, 17 were treated with an ARFOX regimen, which is the experimaltal regimen in the ongoing Phase III AGENT-study.
A best ORR of 59% was observed in the ARFOX regimen group versus 50% in the ARFIRI regimen group, despite that 53% of the patients had a right-sided tumor location and 24% were carrying a BRAF mutation 4,5. In the general CRC population and in historical control first line mCRC Phase III trials, a percentage of approximately 30-40% 1,2,3 right-sided tumors are seen and around 10% of the patients carry a BRAF mutation. Both right-sided tumor location and BRAF mutations are historically known as poor prognostic factors 4,5,6,7,8 and the best ORR in these patient populations in the first line mCRC setting treated with either FOLFOX or FOLFIRI historically generates best ORR in the range of ~40% 1,2 and 15-20% 9,10, respectively.
The average ORR based in pivotal Phase III trials considered in a recent meta-analysis/review by Giuliani & Bonetti (2018) 11 indicates that FOLFOX regimens generates 45% best ORR and FOLFIRI regimens generates 40% best ORR in historical non-selected patient population (all-comer) first line mCRC populations.
The safety extension cohorts comprised a total of 43 patients. Of these, 12 patients were either not evaluated at 8 weeks (not included in the per protocol group) or beyond 8 weeks of treatment with a CT-scan (follow up after 8 weeks was not mandatory), thus not followed until best ORR.
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