Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 2:38 AM
Ignite Modification Date:
2025-12-25 @ 2:38 AM
NCT ID:
NCT07021534
Brief Summary:
This is a single-center, single-arm, open-label, dose-escalation clinical study to evaluate the safety and preliminary efficacy of NKG2D CAR-NK cells followed by NKG2D CAR-T cells in patients with advanced solid tumors (e.g.,colorectal cancer) with liver metastases who have failed standard treatments.
The study primarily focuses on determining the maximum tolerated dose and recommended phase II dose through sequential cohort dose escalation, while secondarily characterizing the pharmacokinetic parameters and collecting initial efficacy data regarding tumor response.
This investigation comprehensively evaluates the pharmacodynamic and pharmacokinetic profile of NKG2D CAR cellular therapy through three primary objectives: (1) systematic monitoring of treatment-emergent adverse events and clinically significant laboratory parameter deviations; (2) assessment of antitumor activity with correlative biomarker analysis; and (3) characterization of cellular kinetics including biodistribution patterns, and mechanistic pathways of therapeutic activity. The protocol clarifies cellular persistence and functional regulation within the tumor microenvironment by longitudinal monitoring of cytokine release and using advanced molecular tracking methods.
Detailed Description:
This study plans to enroll 9-18 patients with advanced solid tumors (e.g.,colorectal cancer) with liver metastases who have failed standard treatments during a dose-finding phase (Phase IA ). CAR immune cell therapy will be administered primarily via hepatic artery infusion and intravenous infusion. Based on previous experience, hepatic artery infusion will deliver a fixed dose of 3×10\^9 NKG2D CAR-NK cells. After catheterization, the catheter will remain indwelling for two days to allow two NKG2D CAR-NK infusions: 1×10\^9 cells on Day 0 and 2×10\^9 cells on Day1. The preferred source for CAR-NK cells is umbilical cord blood. However, if post-treatment evaluation shows that a patient's results do not meet expected criteria, investigators will adjust the strategy based on clinical circumstances and switch to autologous peripheral blood as the source of CAR-NK cells to ensure optimal therapeutic efficacy. Investigators will determine whether to initiate autologous NKG2D CAR-T cell reinfusion 1-2 weeks post-intervention based on clinical response. The CAR-T cells will be administered via two consecutive intravenous infusions over two days, with dose escalation following the classical "3+3" schema.
Based on prior experience, rapid titration dose escalation will initially proceed with 1 patient per cohort. The starting dose is set at 1.5×10\^7 cells/kg. If grade ≥2 CRS or related AEs occur, the study will switch to the 3+3 dose escalation mode. If no such events occur, escalation will follow 3×10\^7 cells /kg, 5×10\^7 cells /kg, and 7×10\^7 cells /kg doses using the 3+3 design, with 3 patients enrolled per dose level. Each CAR-T intravenous infusion involves two consecutive administrations over two days. Approximately two weeks after the first cycle of CAR-T infusions, a second cycle of two consecutive CAR-T infusions will be administered over two days using the same dose as the first cycle.The imaging re-examination will be performed approximately two weeks after completing one cycle of cell reinfusion (i.e., post-second CAR-T infusion), serving as the observation window for safety indicators such as dose-limiting toxicity (DLT) graded per NCI-CTCAE v5.0 criteria in the combined immunotherapy. Based on imaging findings, safety data, and investigator evaluation, subsequent indications for interventional therapy and continued autologous reinfusion will be determined.
The trial progresses through sequential Phase IA (dose-finding) and Phase IB (dose-expansion) stages. Phase IA cessation triggers include either confirmation of Recommended Phase II Dose (RP2D) or investigator-verified favorable therapeutic index at any dose level.
An interim analysis will be conducted upon Phase IA completion, followed by submission of an ethical amendment application prior to initiating Phase IB.
The interim analysis incorporates exploratory subgroup analyses stratified by factors including tumor histology, NKG2D ligand expression levels, prior treatment regimens, baseline tumor burden, tumor markers, peripheral blood granulocyte-to-lymphocyte ratio, and metastatic sites during dose escalation.
Following the completion of Phase IA, investigators may identify tumor types likely responsive to NKG2D CAR immune cell therapy based on preliminary data and existing literature, and select patients with potentially responsive tumor types for expanded cohort enrollment, treating advanced solid tumor patients with liver metastases who have failed standard treatments. In Phase IB, investigators will conduct multiple dose expansion cohorts , divided into colorectal cancer, gastric cancer, esophageal cancer, and other cohorts, with 9-18 cases each.
Study:
NCT07021534
Study Brief:
Protocol Section:
NCT07021534