Napabucasin/FOLFIRI Shows No Benefit in OS for Patients With mCRC

The addition of napabucasin to the FOLFIRI regimen (Irinotecan, fluorouracil (5-FU), and folinic acid [leucovorin]) with or without bevacizumab (Avastin) did not demonstrate improvement in overall survival (OS) when given as treatment of patients with metastatic colorectal cancer (mCRC), missing the primary end point of the phase 3 CanStem303C study (NCT02753127).¹

"Patients with metastatic colorectal cancer have a high unmet medical need, and our hope was to develop a new treatment option for this population. We are disappointed with the results of this Phase 3 trial,” said Patricia S. Andrews, chief executive officer and Global Head of Oncology, Sumitomo Dainippon Pharma Oncology, in a statement.

CanStem303C is a multicenter, open-label, randomized study, which enrolled 1,250 patients with previously treated mCRC to assess the efficacy and safety of the napabucasin combination. Those enrolled were randomized 1:1 and were dosed with napabucasin 240 mg twice daily and FOLFIRI. In the comparator arm, patients received FOLFIRI alone. FOLFIRI dosing consisted of irinotecan 180 mg/m2 in combination with leucovorin 400 mg/m2 given intravenously along with 5-FU 1200 mg/m2 per day. The patients for whom bevacizumab was administered received the standard dose of 5 mg/kg.

The coprimary end points explored in the study were OS in the overall study population as well as among patients who tested positive for the biomarker pSTAT3. The prespecified hazard ratio for the determination of OS benefit in this study was 0.80 or an improvement from 12.54 to 15.68 months. The study also evaluated secondary end points which included OS in the patients with pSTAT3 positive tumors, progression-free survival (PFS) in the intention-to-treat (ITT) population, OFS in the biomarker-positive group, objective response rate. and disease control rate in the ITT and biomarker-positive groups, safety, and quality of life. Investigators also collected blood and tumor samples to test pharmacokinetic activity and perform biomarker analyses on the patients.²

In the study, stratification was based on geography, time to progression on first-line therapy, RAS mutation status, receipt of bevacizumab as part of the study, and primary tumor location.

Eligible patients included those who are 18 years of age or older with histologically confirmed advanced mCRC, an ECOG performance status of 0 or 1, and adequate laboratory tests at screening. Patients were also required to be fit for chemotherapy.

No data have been reported from this study to data, but the developer announced plans to publish the full results. It was revealed that no new safety signals were observed in the study and the adverse events seen were consistent with previous data. The AEs included diarrhea, nausea, vomiting, and abdominal pain.¹

_References:

_{1. Sumitomo Dainippon Pharma Oncology announces phase 3 canstem303c study of napabucasin fails to reach primary endpoints in patients with previously treated metastatic colorectal cancer. News release. February 9. 2021. Accessed February 10, 2021.}

_{2. Grothey A, Shah MA, Yoshino T, et al. CanStem303C trial: A phase III study of napabucasin (BBI-608) in combination with 5-fluorouracil (5-FU), leucovorin, irinotecan (FOLFIRI) in adult patients with previously treated metastatic colorectal cancer (mCRC). J Clin Oncol. 2017; 35(suppl 15). doi: 10.1200/JCO.2017.35.15_suppl.TPS3619}