To find the highest dose of NK cells that can be given by vein and intraperitoneally (given directly into the abdominal cavity) in combination with cetuximab to patients with colorectal cancer that has spread to the peritoneum.
Subjects must be 18 years or older. Because no dosing or adverse event data are currently available on the use of IP/IV TROP2 CAR/IL-15 TGFBR2 KO NK Cell Therapy + Cetuximab in participants 3 liver metastases, >5 lung metastases, or >8 metastases combined between all extraperitoneal sites will not be included even in the setting of measurable peritoneal disease. If a participant has peritoneal-predominant disease with ≤ 8 total extraperitoneal metastases, they may be included at the discretion of the PI.
Subjects must be at least 4 weeks from their last dose of systemic cytotoxic chemotherapy at the time of their diagnostic laparoscopy (DL)/IP catheter placement or 6 weeks if the chemotherapy regimen included Bevacizumab. Participants must be at least 4 weeks from their last dose of systemic cytotoxic chemotherapy at the time of their lymphodepleting (LD) chemotherapy.
Subjects must be willing to undergo DL and IP catheter placement along with scheduled peritoneal fluid/peripheral blood draws and biopsies.
Subjects must have adequate organ function as defined in the following table. Specimens must be collected within 10 days prior to the start of study treatment.
Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with screening visit through 4 months after last dose of trail treatment (TROP2 CAR/IL-15 TGFBR2 KO NK cell therapy). If a WOCBP has a positive urine pregnancy test within 72 hours prior to administration of LD chemotherapy that cannot be confirmed as negative, a serum pregnancy test will be required.
Participants with BRAFV600E mutated tumors (determined by Next Generation Sequencing, NGS) will be excluded.
Has received systemic anti-cancer therapy within 4 weeks of their scheduled diagnostic laparoscopy (DL)/IP catheter placement or 6 weeks if the regimen included Bevacizumab. Or has received systemic chemotherapy of any kind within 4 weeks prior to the time of their lymphodepleting (LD) chemotherapy.
Participants must have recovered from all AEs due to previous therapies to Grade ≤1 or baseline. Participants with Grade ≤2 neuropathy, alopecia, or other AEs may be deemed eligible at the discretion of the PI. If a participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
Single group
Cyclophosphamide
DrugGiven by IV
Fludarabine
DrugGiven by IV
Cetuximab
DrugGiven by IV
NK Cells
DrugGiven by IV and IP
Safety and adverse events (AEs
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Click on the lead sponsor to view all of their trials.
