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Patients will receive neoadjuvant treatment with mFOLFOXIRI plus cadonilimab for 6 cycles before surgey

Patients will receive neoadjuvant mFOLFOX6 chemotherapy every two weeks for 6 cycles before surgery.

Patients will receive neoadjuvant mFOLFOXIRI chemotherapy every two weeks for 6 cycles before surgery.

Cadonilimab（AK104）6mg/kg, intravenous d for 60 minutes, followed by mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) every 2 weeks for 6 cycles before surgery

mFOLFOXIRI + Cadonilimab

mFOLFOX6 (oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) every 2 weeks for 6 cycels before surgery

mFOLFOX6

mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) every 2 weeks for 6 cycles before surgery

mFOLFOXIRI

Yanhong Deng, Ph.D

Jianwei Zhang, Ph.D

Yanghong Deng, PhD

Yanhong Deng, PhD

Neoadjuvant chemoradiotherapy (CRT) followed by total mesenteric excision (TME) and adjuvant chemotherapy was the standard of treatment for locally advanced rectal cancer (LARC) in the past two decades. The main obstacles for improving survival benefit of LARC was distant metastasis. Recently, total neoadjuvant therapy (TNT) had been recommended as new preferred option for LARC. Induction chemotherapy with FOLFOXIRI followed by CRT or short-course radiotherapy followed by FOLFOX chemotherapy had improved survival benefit for LARC.

Neoadjuvant immunotherapy had also been explored in pMMR patients with CRC. In the NICHE trial, neoadjuvant therapy with 2 dose of nivolumab and 1 dose of ipilimumab led to 29% of pathological response and 13% of pCR. Cadonilimab (AK104) was a PD-1/CTLA-4 bi-specific antibody. Here, we tried to explore the efficacy of Neoadjuvant Treatment With mFOLFOXIRI with or without Cadonilimab (AK104) Versus mFOLFOX6 in LARC.

This study was a prospective, randomized, uncontrolled phase II trial to evaluate the efficacy of mFOLFOXIRI combined with AK104 neoadjuvant therapy versus mFOLFOX6 neoadjuvant therapy in LARC.

The inclusion criteria: locally advanced colon cancer (T3\>5mm or T4 on enhanced CT assessment, with distant metastasis excluded); Locally advanced rectal cancer (pelvic MR assessment as stage ii-iii, less than 12cm from the anal margin, no distant metastasis), primary tumor location and TNM stage were stratified factors.

Group A: mFOLFOXIRI combined with Cadonilimab (AK104) for 6 cycles before surgery

Group B: 6 cycles of neoadjuvant chemotherapy with mFOLFOX6 before surgery

Group C: 6 cycles of neoadjuvant chemotherapy with mFOLFOXIRI before surgery

All groups were re-evaluated after 3 cycles and 6 cycles of treatment. If surgery was feasible after multidisciplinary evaluation, TME resection was performed, and adjuvant treatment was performed according to standard treatment after operation. For locally advanced rectal cancer, preoperative pelvic enhanced MRI was used to evaluate tumor regression after 6 cycles of preoperative treatment. For patients who still had MRF+ and/or T4 after treatment, additional short-course radiotherapy was allowed.

Neoadjuvant Treatment With mFOLFOXIRI Plus Cadonilimab (AK104) Versus mFOLFOX6 in Locally Advanced Colorectal Cancer

Neoadjuvant Treatment With mFOLFOXIRI Plus Cadonilimab (AK104) Versus mFOLFOX6 Alone in Locally Advanced Colorectal Cancer: a Randomized Control Phase II Study (OPTICAL-2)

Proportion of patients experiencing a pCR to preoperative treatment in each group

The proportion of patients experiencing a major pathological response (≤10% of residual viable tumor in the surgical specimen) to preopeartive treatment in each group

Defined as the time from randomization to relapse, metastasis or death from any cause.

Defined as the time from randomization to local recurrence.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neoadjuvant Treatment With mFOLFOXIRI Plus Cadonilimab (AK104) Versus mFOLFOX6 in Locally Advanced Colorectal Cancer	NCT05571644	Colorectal Canc...	mFOLFOXIRI + Ca... mFOLFOX6 mFOLFOXIRI	18 Years - 70 Years	Sun Yat-sen University
Neoadjuvant Treatment With mFOLFOXIRI Plus Cadonilimab (AK104) Versus mFOLFOX6 in Locally Advanced Colorectal Cancer	NCT05571644	Colorectal Canc...	mFOLFOXIRI + Ca... mFOLFOX6 mFOLFOXIRI	18 Years - 70 Years	Sun Yat-sen University

Spots Global Cancer Trial Database for cadonilimab (ak104)