Dose Escalation and Dose Expansion Phase I Study to Assess the Safety and Clinical Activity of Multiple Doses of NKR-2 Administered Concurrently With FOLFOX in Colorectal Cancer With Potentially Resectable Liver Metastases

NCT03310008 | Unknown Phase 1 DMC

• 1 other identifier: CYAD-N2T-003
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

Brief Summary

SHRINK (Standard cHemotherapy Regimen and Immunotherapy with NKR-2) is an open-label Phase I study to assess the safety and clinical activity of multiple administrations of autologous NKR-2 cells administered concurrently with a standard chemotherapy treatment (FOLFOX) in potentially resectable liver metastases from colorectal cancer. The trial will test three dose levels. At each dose, the patients will receive three successive administrations, two weeks apart, NKR-2 cells. The study will enroll up to 36 patients (dose escalation and expansion phases).

Conditions

Colon Cancer Liver Metastasis

Outcome Measures

Primary Outcomes (2)

• The occurrence of Dose Limiting Toxicities (DLT) in all patients during the study treatment until 14 days after the first NKR-2 study treatment administration

  DLT refers to any Grade 3 or higher toxicity or any Grade 2 or higher autoimmune toxicity that is experienced during treatment and within 14 days following the first NKR-2 dose, is new and at least possibly related to NKR-2 study treatment administered concurrently with chemotherapy

  up to resection (up to day 99 to day 126)

• The objective response rate (ORR) before resection as measured by RECIST (version 1.1)

  The objective response rate (ORR) is defined as the sum of the proportions of patients achieving CR or PR. The occurrence of ORR before resection will be reported.

  up to resection (up to day 99 to day 126)

Secondary Outcomes (9)

• The occurrence of AEs and SAEs and any toxicity corresponding to DLT definition during the study treatment until resection visit

  up to resection (up to day 99 to day 126)

• The occurrence of surgery complications and the wound healing status until 60 days after resection visit

  until 60 days after resection

• The clinical benefit rate (CBR) before resection

  up to resection (up to day 99 to day 126)

• The occurrence of mixed response (MR) before resection

  up to resection (up to day 99 to day 126)

• The resection rate

  resection (day 99 to day 126)

Study Arms (4)

Dose level 1 (escalation

EXPERIMENTAL

The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.

Biological: NKR-2 cells

Dose level 2 (escalation)

EXPERIMENTAL

The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.

Biological: NKR-2 cells

Dose level 3 (escalation)

EXPERIMENTAL

The dose escalation arm will use a 3+3 design to determine the maximum tolerated dose.

Biological: NKR-2 cells

Recommended dose level (expansion)

EXPERIMENTAL

The dose expansion arm will use the maximum tolerated dose.

Biological: NKR-2 cells

Interventions

NKR-2 cells BIOLOGICAL

The intervention will consist of an infusion of NKR-2 cells administered concurrently to a standard chemotherapy every 2 weeks (14 days) for a total of 3 infusions within 4 weeks (28 days).

Also known as: NKG2D CAR-T cells

Dose level 1 (escalation; Dose level 2 (escalation); Dose level 3 (escalation); Recommended dose level (expansion)

Eligibility Criteria

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

You may qualify if:

• Men or women ≥ 18 years old at the time of signing the ICF
• Patients with histologically proven colorectal adenocarcinoma with potentially resectable liver metastases,
• No previous chemotherapy for metastatic CRC,
• The patient is due to receive first-line metastatic chemotherapy regimen with FOLFOX as a neoadjuvant
• The patient must have an ECOG performance status 0 or 1
• The patient must have sufficient bone marrow reserve, hepatic and renal functions
• Detailed disease specific criteria exist and can be discussed with contacts listed below

You may not qualify if:

• Patients who have received another cancer therapy within 2 weeks before the planned day for the apheresis
• Patients who receive or are planned to receive any other investigational product within the 3 weeks before the planned day for the first NKR-2 administration
• Patients who are planned to receive concurrent growth factor, systemic steroid or other immunosuppressive therapy or cytotoxic agent, other than the treatment authorized per protocol
• Patients who underwent major surgery within 4 weeks before the planned day for the first treatment
• Patients with uncontrolled intercurrent illness or serious uncontrolled medical disorder
• Patients who have received a live vaccine within 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 (4)

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

Location

UZ Leuven

Leuven, 3000, 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: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Biological: NKR-2 cells The intervention will consist of an infusion of NKR-2 cells administered concurrently to a standard chemotherapy every 2 weeks (14 days) for a total of 3 infusions within 4 weeks (28 days). Other Name: NKG2D CAR-T cells

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: October 16, 2017
• Study Start: August 7, 2017
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2021
• Last Updated: June 16, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (4)