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

NCT03370198 | Terminated Phase 1 DMC

• 1 other identifier: CYAD-N2T-004
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Colon Cancer Liver Metastasis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• The occurrence of AEs and SAEs during the study treatment until 30 days after the last study treatment administration (Visit Day 57)

  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))

  through study completion (up to month 24)

• The occurrence and duration of clinical benefit (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)

  through study completion (up to month 24)

• The resection rate at Visits Day 57 and Month 3

  At visits Day 57 and Month 3

Study Arms (3)

Dose-level 1

EXPERIMENTAL

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

Dose-level 2

EXPERIMENTAL

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

Dose-level 3

EXPERIMENTAL

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

Interventions

NKR-2 cells BIOLOGICAL

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)

Also known as: NKG2D CAR-T cells

Dose-level 1; Dose-level 2; Dose-level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celyad Oncology SA: lead

Study Sites (1)

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Study Officials

• Frédéric Lehmann, MD

  Celyad Oncology SA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: December 12, 2017
• Study Start: October 11, 2017
• Primary Completion: January 15, 2018
• Study Completion: December 15, 2018
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)