This Phase II study will recruit 17 colorectal cancer patients with liver-dominant metastases. All recruited patients will receive Sotevtamab at a dose of 800 mg once weekly for 6 cycles combined with FOLFOX once every 2 weeks for the first 4 cycles followed by liver metastases resection surgery with or without primary cancer resection. One cycle of treatment will consist of 14 days (2 weeks).
This is an open-label, single-arm, single-center proof-of-concept Phase II trial of sotevtamab in combination with FOLFOX-based preoperative neoadjuvant systemic chemotherapy in participants with resectable liver-dominant metastases and candidate to neoadjuvant FOLFOX followed by partial hepatectomy. Approximately 17 participants will be enrolled in this trial and will receive 4 cycles of FOLFOX (Cycle 1 to Cycle 4) as preoperative systemic chemotherapy and 6 cycles of sotevtamab (Cycle 1 to Cycle 6). One cycle of treatment will consist of 14 days (2 weeks). Sotevtamab will be administered by intravenous (IV) infusion at 800 mg on Day 1 and Day 8 of each cycle. FOLFOX will be administered on Day 1 of Cycle 1 to Cycle 4 as follows: oxaliplatin 85 mg/m² IV infusion + leucovorin 400 mg/m² IV infusion + 5-Fluorouracil (5-FU) 400 mg/m² IV bolus + 5-FU 2400 mg/m² continuous IV infusion over 46 hours. Participants will undergo liver metastasis resection with or without primary cancer resection following recovery from preoperative neoadjuvant systemic chemotherapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Sotevtamab is an inhibitor of the epithelial to mesenchymal transition. It is a fully humanized monoclonal antibody of IgG2 isotype against tumor-associated secreted clusterin (TA-sCLU)
FOLFOX is a chemotherapy regimen for treatment of colorectal cancer, made up of the drugs folinic acid, fluorouracil, and oxaliplatin.
Centre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, Canada
RECRUITINGRubbia-Brandt score at surgery
To characterize the pathological response of resected colorectal liver metastases as determined by the Rubbia-Brandt score. The Rubbia-Brandt score distinguishes five Tumor Regression Grades (TRG1-TRG5) according to the presence of residual tumor cells and extent of fibrosis.
Time frame: 16-18 weeks
Treatment-Emergent Adverse Events
Incidence, relatedness, and severity of treatment-emergent adverse events
Time frame: 14-16 weeks
Objective Response Rate (ORR)
To determine the objective response rate (ORR) per RECIST 1.1
Time frame: 9-10 weeks
Quantity of circulating tumor DNA (ctDNA)
To evaluate minimal residual disease detection rate after colorectal liver metastases resection
Time frame: Weeks 1 and 5, at surgery and post-surgery
Sotevtamab concentrations in plasma
To determine the pharmacokinetics (PK) of sotevtamab in the trial population
Time frame: Weekly for 12 weeks and between Weeks 14 and 16
Presence of ADA
To evaluate the presence of anti-sotevtamab antibodies (ADA) in the trial population and their effect on exposure and tumor response
Time frame: Weeks 1, 3, 8 and between Weeks 14 and 16
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