570P - A phase II clinical study of fruquintinib (Fru) combined with toripalimab (Tor) and short-course radiotherapy (SCRT) as neoadjuvant therapy for locally advanced rectal cancer (LARC)

Background

Pathological complete response (pCR) rate for conventional chemoradiotherapy regimens as neoadjuvant therapy for LARC were not that satisfactory. Fru and SCRT have both shown synergistic effects in combination with immunotherapy in colorectal cancer. We conducted this study to assess the safety and efficacy of the combination of Fru and Tor with SCRT as neoadjuvant therapy for LARC.

Methods

This is a prospective, single-arm study. 40 pts with T3-4 and/or N+ LARC will be included. Enrolled pts will receive Fru 5mg po, d1-d14, Tor 240mg i.v, d1, q3w for 4 cycles. SCRT (5 Gy x 5) was simultaneously conducted d1-d5 during the 2^nd cycle. Eligible pts will undergo TME surgery within 2-4 weeks after completing neoadjuvant therapy. The primary endpoint was pCR rate. Based on Simon’s 2 stage design, 40 pts were required with a two side α of 0.05 and a power of 80%, estimating a desirable pCR 30% and an unacceptable pCR 12%.

Results

As of Feb 2024, 23 pts were enrolled, and their baseline characteristics are presented in the table. 22 (95.7%) pts presented a high-risk profile, marked by factors such as cT4, cN2, EMVI+, or MRF+. 19 pts completed the neoadjuvant treatment, and 16 pts underwent TME surgery, with a R0 resection rate of 100%. Anal preservation rate reached 75% (12/16). Six pts achieved pCR, yielding a pCR rate of 37.5% (95% CI: 13.8%-61.2%). Additionally, 10 (62.5%) pts achieved tumor regression grade (AJCC) of 0/1. The most common treatment related adverse events (TRAEs) included hypertension (56.5%), thyroid dysfunction (43.5%), and palmar-plantar erythrodysesthesia syndrom (34.8%). Grade 3 TRAEs include hypertension (26.1%), platelet count decreased (4.3%), ALT increased (4.3%) and diarrhea (4.3%). No grade 4/5 TRAEs was observed. This trial is ongoing. Table: 570P

Conclusions

Combination of Fru, Tor and SCRT has shown a potential efficacy for the neoadjuvant therapy of LARC with a tolerable toxicity.

Clinical trial identification

NCT05763927.

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.