Abstract 485P
Background
The standard third-line treatment of metastatic colorectal cancer (mCRC) is regorafenib, fruquintinib, or TAS-102. However, the efficacy was not satisfied. We conducted a phase Ib /Ⅱa clinical study to evaluate the safety and efficacy of fruquintinib plus cetuximab in mCRC（TPS151, 2021 ASCO GI） This time we reported the phase Ib dose-escalation study results.
Methods
This is a single-center, non-random, prospective, dose-escalation (3 + 3 design), exploratory study. Eligible patients were diagnosed with advanced RAS/BRAF wild-type colorectal cancer and had received at least two prior regimens. The starting dose of fruquintinib was 4 mg once daily (QD) in a 28-day cycle (3 weeks on/1 week off) plus cetuximab. If tolerable, fruquintinib was escalated to 5 mg. If not tolerable, the fruquintinib dose was reduced to 3 mg. The dose of cetuximab is 500mg/m2 every two weeks. 6-9 patients were involved in this study. Adverse events（AEs） were graded according to NCI-CTCAE v4.0. Drug limiting toxicities(DLTs) were evaluated in cycle 1. The response was assessed using RECIST v1.1 q8 wks. The purpose is to confirm the safety and recommended phase II dose (RP2D).
Results
As of Feb 2021, 7 patients were involved. 3 patients received fruquintinib 4 mg and 4 received fruquintinib 5 mg. One DLTs of grade 3 acneiform rash was observed in 1/3 patients at the 4 mg dose. Two DLTs with grade 3 hypertension and two DLTs with grade 3 proteinuria were confirmed at the 5 mg dose level in 3/4 patients. The RP2D is fruquintinib 4 mg QD (3 weeks on/1 week off) plus cetuximab 500mg/m2 every two weeks. The most common treatment-related AEs were hypertension (3/7), proteinuria (3/7), acneiform rash (3/7), creatinine elevation（2/7）, hypoproteinemia (2/7), hemorrhinia (2/7), fatigue (2/7), anemia(2/7), elevated alkaline phosphatase(2/7), elevated aspartic transaminase (1/7) and dry skin (1/7). Evaluation in 7 treated patients showed 4 cases were stable disease (SD) and 3 cases were progressive disease (PD).
Conclusions
Cetuximab combined with fruquintinib showed acceptable anti-tumor activity in CRC with resistance to at least two prior regimens. No unexpected toxicities were observed.
Clinical trial identification
ChiCTR2000038227.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.