113P - Phase I/II study of capecitabine(C)/oxaliplatin(O)/irinotecan(I) combined with bevacizumab(B) in the first-line treatment of metastatic colorectal cancer (mCRC)

Background

Our real-world data show high response rates with the COIB regimen for mCRC (Liu, Ou et al. 2022). But the appropriate dosage needs to be carefully explored. Therefore, we designed this prospective phase I/II study to determine the efficacy and tolerability of this combination regimen in the first-line treatment of mCRC.

Methods

This study consists of dose escalation (DES) and dose expansion (DEX). The primary objective in DES phase was to evaluate safety and tolerability of I combined with COB, followed by a DEX phase to verify the safety and tolerability profile of the combination therapy. Primary endpoints included recommended phase ll dose (RP2D) and efficacy of the combination. Other end points included exploratory biomarkers of drug activity. I was administered once a day (QD) at two dose levels (150mg/㎡ or 165mg/㎡) in combination with C (1g/㎡ bid, day 1-7)+ O (85mg/㎡, day 1)+B (5mg/kg, day 1), every 14 days (Q2W).

Results

As of August 13, 2023, 97 pts (median age: 58 years; 30% female; 77% left-sided intestine; 43 KRAS mutation, 6 NRAS mutation, 4 BRAF mutation, 31 wild type, 13 unknown) were treated (6 in DES, 91 in DEX). None of the 3 pts in irinotecan dose level 1 or 3 pts in irinotecan dose level 2 of DES had dose limiting toxicities (DLTs), and irinotecan (165mg/㎡, day1) was the RP2D. Treatment-related adverse events (TRAEs) of any grade occurred in 87 (89.7%) pts. TRAEs of grade ≥ 3 were mainly myelosuppression (20 pts, 20.6%) and diarrhea (10 pts, 10.3%). There were no fatal TRAEs. Of 90 pts evaluable for response, Objective response rate (ORR) was 73.3% (95% CI: 64.1%, 82.4%), Disease control rate (DCR) was 98.8% (95% CI: 96.7%, 100.0%).22 patients were successfully transformed and underwent radical resection, No evidence of disease (NED) rate was 22.7% (95% CI: 14.4%, 31.0%). With median follow-up of 17.0 months, 46 pts had progressive disease, median progression free survival (PFS) was 13.0 months（95%CI: 10.8, 19.3), overall survival (OS) are not yet mature. Detection biomarkers of drug activity is in progress.

Conclusions

The RP2D of irinotecan in COIB regimen is 165 mg/m2. The efficacy of the regimen is promising with well tolerance.

Clinical trial identification

NCT04380103.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Development Project of Medical Oncology Key Foundation of Cancer Hospital Chinese Academy of Medical Sciences (CICAMS-MODP2022002).

Disclosure

All authors have declared no conflicts of interest.