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

• ClinicalTrials.gov Identifier: NCT03370198
• Recruitment Status: Unknown
• First Posted: December 12, 2017
• Last Update Posted: June 18, 2020
• Sponsor: Celyad Oncology SA
• Information provided by (Responsible Party): Celyad Oncology SA

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Colon Cancer Liver Metastasis	Biological: NKR-2 cells	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: There will be a hepatic transarterial administration of NKR-2 every 2 weeks for a total of 3 administrations within 4 weeks (28 days). Three dose-level will be assessed (dose escalation with 3 dose-levels or 3 cohorts).
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: October 11, 2017
• Actual Primary Completion Date: January 15, 2019
• Estimated Study Completion Date: December 15, 2020

Arms and Interventions

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 Name: 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 Name: 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 Name: NKG2D CAR-T cells

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. The occurrence of AEs and SAEs during the study treatment until 30 days after the last study treatment administration (Visit Day 57) [ Time Frame: From study treatment start (Day 1) till 30 days after the last study treatment administration (Day 57) ]
   AEs and SAEs collection
2. The occurrence and duration of objective clinical response (complete response (CR), partial response (PR)) [ Time Frame: through study completion (up to month 24) ]
   Complete response (CR), partial response (PR)
3. The occurrence and duration of clinical benefit (complete response (CR), partial response (PR) and stable disease (SD)) [ Time Frame: through study completion (up to month 24) ]
   Complete response (CR), partial response (PR) and stable disease (SD)
4. The occurrence and duration of mixed response (MR) [ Time Frame: through study completion (up to month 24) ]
   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.
5. The resection rate at Visits Day 57 and Month 3 [ Time Frame: At visits Day 57 and Month 3 ]
   Assessment of R0, R1 and R2 resections
6. The progression-free survival (PFS) [ Time Frame: through study completion (up to month 24) ]
   The progression-free survival (PFS) is defined from registration in the study to the disease progression or death from any cause
7. The event-free survival (EFS) [ Time Frame: through study completion (up to month 24) ]
   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
8. The overall survival (OS). [ Time Frame: through study completion (up to month 24) ]
   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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Belgium

Institut Jules Bordet

Brussels, Belgium, 1000

Sponsors and Collaborators

Celyad Oncology SA

Investigators

• Principal Investigator: Frédéric Lehmann, MD; Celyad Oncology SA

More Information

• Responsible Party: Celyad Oncology SA
• ClinicalTrials.gov Identifier: NCT03370198
• Other Study ID Numbers: CYAD-N2T-004
• First Posted: December 12, 2017
• Last Update Posted: June 18, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasm Metastasis; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Neoplastic Processes; Pathologic Processes; Liver Diseases