639P - First report of the safety/tolerability and preliminary antitumor activity of fruquintinib plus capecitabine versus capecitabine as maintenance treatment for metastatic colorectal cancer: An open-label, randomized phase Ib/II study

Background

Maintenance therapy with fluoropyrimidines (such as capecitabine [Cap]) following induction therapy is wildly recommended to unresectable mCRC patients. Fruquintinib (Fru) is a highly selective inhibitor of VEGFR1/2/3 with conspicuous safety and efficacy in mCRC. We sought to evaluate and compare the therapeutic potential of Fru plus Cap (FC) versus Cap as maintenance therapy for mCRC.

Methods

Eligibility criteria included: histologically confirmed mCRC (stage IV), age ≥ 18 years, ECOG PS 0-2, achieved disease control (including CR/PR and SD) after ≥ 6 cycles of first-line standard chemotherapy and still unresectable. In safety lead-in phase (SP), patients (pts) were orally administered with Fru (4 mg, QD, d1-21, Q4W) plus Cap (850 mg/m², BID, d1-7 and d15-21, Q4W). In expansion phase, pts were randomized in a 1:1 ratio between FC (Arm A) and Cap (Arm B) only. The primary objectives were to characterize safety, confirm the recommended phase 2 dose (RP2D; in phase SP), and evaluate the efficacy (in phase EP).

Results

As of April 24, 2023, 22 pts were enrolled (SP: n = 6; EP: Arm A/B n/n = 7/7). In phase SP, 1 pt experienced DLT of grade 3 oral mucositis. The treatment emergent AEs (TEAEs, Grade ≥3) were hypertension (1/6), oral mucositis (1/6), voice alteration (1/6), small intestinal obstruction (1/6) and blood bilirubin increased (1/6). After full consideration about patient’s tolerance and safety, the RP2D of Fru was adjusted from 4mg to 3mg through charrette. In Arm A, the most common TEAEs (Grade ≥3) were merely hypertension and leukopenia. Intriguingly, these results provided further evidence that reducing RP2D from 4 mg to 3mg can ensure the safety and tolerance. In 6 evaluable pts of phase SP, the DCR was 100% while the mPFS was immaturity, but 3 pts showed the PFS of ≥ 6 months (7.5, 8.6, 8.9 mon, respectively).

Conclusions

The combination of fruquintinib plus capecitabine demonstrated an acceptable tolerability profile. Preliminary antitumor activity was observed in pts with mCRC that revealed promising efficacy and safety as a first-line maintenance therapy. Dose expansion is ongoing at the RP2D in dedicated mCRC.

Clinical trial identification

NCT05451719.

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.