TROP2-Directed CAR-NK

Primary Objective and Endpoints Objective: Determine the safety, and Maximum Tolerated Dose (MTD), Recommended Phase 2 Dose (RP2D), schedule of iterative delivery of dual administration of IP/IV TROP2 CAR/IL-15 TGFBR2 KO NK cells Cell Therapy + IV Cetuximab

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.

Registro actualizado en ClinicalTrials.gov →

• 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.
• Participant s must have histologically confirmed microsatellite stable (MSS) CRC-related PM that is not amenable to curative resection (participant determined not to be a candidate for CRS +/- HIPEC by surgical oncologist with expertise in peritoneal surface malignancies) and for which standard curative treatment is no longer effective (they have progressed through at least one line of standard systemic chemotherapy and/or are intolerant of systemic chemotherapy in the opinion of their primary medical oncologist). • MSS status must be confirmed either by immunohistochemistry (IHC) or polymerase chain reaction (PCR)-based genetic analysis. Participants with MSI-H tumors are ineligible. • Participant must have never undergone a prior HIPEC operation (CRS without HIPEC is OK) • Participant s with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Criterios de inclusión tal como figuran en el registro, recortados. La lista completa, con las exclusiones, está en el registro actualizado.