Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer (LINK)

An Open-label Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer

The purpose of this study is to test an experimental anti-cancer immunotherapy called NKR-2 (modified T cells), to treat colorectal cancer with unresectable liver metastases. The trial will test three dose levels (dose escalation). At each dose, the patients will receive three successive hepatic transarterial administrations, two weeks apart, of NKR-2 cells. The study will enroll up to 18 patients.

Study Overview

• Status: Terminated
• Conditions: Colon Cancer Liver Metastasis
• Intervention / Treatment: Biological: NKR-2 cells

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The patient must be ≥ 18 years old at the time of signing the ICF.
• The patient must have a histologically proven adenocarcinoma of the colon or rectum.
• The patient must have liver metastases non treatable with curative intent by surgical resection or local ablation at the time of registration.
• The patient must have measurable hepatic metastases defined by RECIST version 1.1 for solid tumors.
• The patient must have received one prior chemotherapy line for metastatic disease and have developed resistance or intolerance to this treatment.
• The patient must have an ECOG performance status 0 or 1.
• The patient must have the bone marrow reserve, hepatic and renal functions

Exclusion Criteria:

• Patients who are presenting evidence of ascites, cirrhosis, portal hypertension, main portal venous tumor involvement or thrombosis as determined by clinical or radiologic assessment.
• Patients who are planned to receive or concurrently receiving any non-cancer-directed investigational agent, or have received a non-cancer directed investigational agent within 3 weeks before the planned day for the first NKR-2 administration.
• Patients who are scheduled to receive concurrent growth factor (except erythropoietin), systemic steroid, other immunosuppressive therapy or cytotoxic agents (systemic or localized) other than the treatment authorized per protocol.
• Patients who underwent major surgery within 4 weeks before the planned day for the first NKR-2 administration.
• Patients who have received a live vaccine ≤ 6 weeks prior to the planned day for the first NKR-2 administration.
• Patients with a family history of congenital or hereditary immunodeficiency.
• Patients with history of any autoimmune disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-level 1; The dose-level 1 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)	Biological: NKR-2 cells; NKR-2 cells will be administered (hepatic transarterial administration) every 2 weeks (14 days) for a total of 3 administrations within 4 weeks (28 days); Other Names: NKG2D CAR-T cells
Experimental: Dose-level 2; The dose-level 2 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)	Biological: NKR-2 cells; NKR-2 cells will be administered (hepatic transarterial administration) every 2 weeks (14 days) for a total of 3 administrations within 4 weeks (28 days); Other Names: NKG2D CAR-T cells
Experimental: Dose-level 3; The dose-level 3 arm will use a 3+3 design. NKR-2 cells will be administered every 2 weeks (14 days) for a total of 3 administrations (hepatic transarterial administrations) within 4 weeks (28 days)	Biological: NKR-2 cells; NKR-2 cells will be administered (hepatic transarterial administration) every 2 weeks (14 days) for a total of 3 administrations within 4 weeks (28 days); Other Names: NKG2D CAR-T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence of DLTs until 14 days after the last NKR-2 study treatment administration (Visit Day 43)	A DLT is defined as any Grade 3 or higher toxicity and any Grade 2 or higher autoimmune toxicity	From study treatment start (Day 1) till 14 days after the last NKR-2 study treatment administration (Day 43)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence of AEs and SAEs during the study treatment until 30 days after the last study treatment administration (Visit Day 57)	AEs and SAEs collection	From study treatment start (Day 1) till 30 days after the last study treatment administration (Day 57)
The occurrence and duration of objective clinical response (complete response (CR), partial response (PR))	Complete response (CR), partial response (PR)	through study completion (up to month 24)
The occurrence and duration of clinical benefit (complete response (CR), partial response (PR) and stable disease (SD))	Complete response (CR), partial response (PR) and stable disease (SD)	through study completion (up to month 24)
The occurrence and duration of mixed response (MR)	The different types of MR are defined according to the following criteria: at least 30% decrease in the longest diameter (or shortest diameter for nodal lesions) occurring in at least one target lesion recorded and measured at baseline. Such response occurring in otherwise SD or PD status of the sum of diameters of target lesions and without the appearance of one or more new lesions will be classified as "MR (SD)", which corresponds to a SD with target lesion regression or "MR (PD)", which corresponds to PD with target lesion regression and, the appearance of new lesion(s) in otherwise PR status of the sum of diameters of target lesions will be classified as "MR (PR)", which corresponds to a PR with new lesion.	through study completion (up to month 24)
The resection rate at Visits Day 57 and Month 3	Assessment of R0, R1 and R2 resections	At visits Day 57 and Month 3
The progression-free survival (PFS)	The progression-free survival (PFS) is defined from registration in the study to the disease progression or death from any cause	through study completion (up to month 24)
The event-free survival (EFS)	The event-free survival (EFS) is defined as the time from registration in the study to any of the following events: progression, local or distant recurrence, or death from any cause	through study completion (up to month 24)
The overall survival (OS).	The overall survival (OS) is defined as the time from registration in the study to death. If death does not occur before the patient's last study visit, then the survival will be censored at the date when patient is known to be alive	through study completion (up to month 24)

Collaborators and Investigators

• Sponsor: Celyad Oncology SA
• Investigators: Principal Investigator: Frédéric Lehmann, MD, Celyad Oncology SA

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2017
• Primary Completion (Actual): January 15, 2018
• Study Completion (Actual): December 15, 2018

Study Registration Dates

• First Submitted: November 8, 2017
• First Submitted That Met QC Criteria: December 6, 2017
• First Posted (Actual): December 12, 2017

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Neoplastic Processes; Neoplasm Metastasis; Liver Neoplasms
• Other Study ID Numbers: CYAD-N2T-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No