NCT05571644

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)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 143 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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). 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 Group D (exploratory cohort): mFOLFOXIRI combined with Cadonilimab (AK104) and fruquintinib for 3 months before surgery (not for randomised) 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.

Conditions

• Colorectal Cancer

Interventions

Type	Name	Description
DRUG	mFOLFOXIRI + Cadonilimab	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
DRUG	mFOLFOX6	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
DRUG	mFOLFOXIRI	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
DRUG	mFOLFOXIRI+AK104+fruquintinib	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, and fruquintinib (3mg Qd, D1-21, Q4W for 3 months) before surgery

Timeline

• Start date: 2023-07-10
• Primary completion: 2025-12-31
• Completion: 2027-08-15
• First posted: 2022-10-07
• Last updated: 2025-07-23

Locations

1 site across 1 country: China