This is a prospective, multicenter, open-label, single-arm Phase II study designed to evaluate the efficacy and safety of total neoadjuvant mFOLFOX6 combined with suvemcitug and enlonstobart in patients with MRI(Magnetic Resonance Imaging)-defined high-risk, mid-rectal, locally advanced rectal adenocarcinoma with pMMR/MSS status. All enrolled participants will receive 6 cycles of mFOLFOX6 plus suvemcitug and enlonstobart every 2 weeks. After 6 cycles, participants will undergo reassessment with pelvic MRI and systemic imaging. Participants who achieve at least 20% tumor regression on MRI without new high-risk radiologic features will continue with 2 additional cycles of mFOLFOX6 followed by radical total mesorectal excision surgery, without routine pelvic radiotherapy. Participants who do not meet the predefined regression threshold or show disease progression will receive long-course chemoradiotherapy with concurrent capecitabine, followed by 3 cycles of mFOLFOX6 and radical surgery.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
52
Oxaliplatin 85 mg/m2 IV over 2 hours on Day 1; leucovorin calcium 400 mg/m2 IV over 2 hours on Day 1; 5-fluorouracil 400 mg/m2 IV bolus on Day 1; 5-fluorouracil 2400 mg/m2 continuous IV infusion over 46-48 hours;every 2 weeks, for 6 cycles during the initial total neoadjuvant treatment phase. Participants meeting the predefined MRI regression criterion will receive 2 additional cycles of mFOLFOX6 before surgery. Participants requiring chemoradiotherapy will receive 3 additional cycles of mFOLFOX6 after long-course chemoradiotherapy before surgery.
Suvemcitug 2 mg/kg IV infusion on Day 1 of each 14-day cycle, every 2 weeks, for 6 doses during the initial total neoadjuvant treatment phase.
Enlonstobart 240 mg IV infusion on Day 1 of each 14-day cycle, every 2 weeks, for 6 doses during the initial total neoadjuvant treatment phase.
Used selectively for participants who do not achieve the predefined interim MRI regression threshold or who show disease progression. 45-50.4 Gy in 25-28 fractions. Oral capecitabine during radiotherapy.
For participants omitting radiotherapy: approximately 2-4 weeks after completion of total neoadjuvant systemic therapy. For participants receiving chemoradiotherapy: after long-course chemoradiotherapy and subsequent mFOLFOX6 treatment, according to investigator assessment.
Department of General Surgery, Zhongshan Hospital, Fudan University
Shanghai, China
Pathologic Complete Response Rate
Time frame: Perioperative : at the time of surgery for pCR(Pathologic Complete Response Rate).
R0 Resection Rate
Time frame: Perioperative : at the time of surgery.
Circumferential Resection Margin Negative Rate
Time frame: Perioperative : at the time of surgery.
Major Pathologic Response Rate
Time frame: Perioperative : at the time of surgery.
Proportion of Participants Receiving Pelvic Radiotherapy
Time frame: At the end of Cycle 6 (each cycle is 14 days)"
Successful Radiotherapy Omission Rate
Time frame: From enrollment to surgery.
Three-Year Disease-Free Survival
Time frame: Up to 3 years after surgery
Quality of life will be evaluated using the European O-rganization for Reasearch and Treatment of Cancer Quality of Life Questionnaire-C30(EORTC QLQ-C30) (range 0-100).
It evaluates the quality of life from 30 aspects, including appetite, mental status, sleep quality, fatigue, etc. The higher scores mean a better quality of life.
Time frame: Baseline, At the end of Cycle 6 (each cycle is 14 days),Perioperative
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