alloSHRINK - Standard cHemotherapy Regimen and Immunotherapy With Allogeneic NKG2D-based CYAD-101 Chimeric Antigen Receptor T-cells

Study Overview
=================
Brief Summary
-----------------
The purpose of the alloSHRINK study is to assess the safety, cell kinetics and clinical activity of CYAD-101 in patients with unresectable metastatic colorectal cancer administered after standard chemotherapy

Detailed Description
-----------------
This Study aims to determine and confirm the recommended dose of the allogeneic CYAD-101 cells after standard FOLFOX or FOLFIRI chemotherapy in patients with unresectable metastatic colorectal cancer

Official Title
-----------------
An Open-label, Phase I Study to Assess the Safety of Multiple Doses of CYAD-101, Administered After Standard FOLFOX or FOLFIRI Chemotherapy in Patients With Unresectable Metastatic Colorectal Cancer

Conditions
-----------------
Unresectable Metastatic Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: CYAD-101
* Drug: FOLFOX
* Drug: FOLFIRI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven metastatic adenocarcinoma of the colon or rectum. Confirmed metastatic unresectable adenocarcinoma of the colon or the rectum. Recurrent/progressing disease after at least one line of systemic therapy for metastatic disease. Unequivocal and measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). FOLFOX segment: Neurotoxicity less than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 from previous chemotherapy. FOLFIRI segment: Documented progressive disease (PD) under FOLFIRI treatment, with or without targeted therapy, given within 3 months prior to study registration. Anti-cancer therapy post FOLFIRI-documented PD prior to study registration is authorized if discontinued at least 7 days before the planned study registration. Radiotherapy is not authorized. The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. The patient must have adequate bone marrow reserve, hepatic, renal, pulmonary and cardiac functions. Exclusion Criteria: The patient has a confirmed or history of tumor involvement in the central nervous system (CNS). Any non-cancer-directed investigational agent within 3 weeks before the planned day for the first CYAD-101 administration. Filgrastim (Granulocyte-Colony-Stimulating Factor [G-CSF]) or similar growth factors within 7 days before the planned day for the first CYAD-101 administration. Prior allogeneic stem cell transplantation, chimeric antigen receptor therapy or other genetically modified T-cell therapy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYAD-101 with FOLFOX<br>Infusion after standard FOLFOX chemotherapy | Drug: CYAD-101<br>* Allogeneic NKG2D-based CYAD-101 Chimeric antigen Receptor T-cells<br>Drug: FOLFOX<br>* 5-FU, leucovorin and oxaliplatin<br>|
| Experimental: CYAD-101 with FOLFIRI<br>Infusion after standard FOLFIRI chemotherapy | Drug: CYAD-101<br>* Allogeneic NKG2D-based CYAD-101 Chimeric antigen Receptor T-cells<br>Drug: FOLFIRI<br>* 5-FU, leucovorin and irinotecan<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of Dose Limiting Toxicities |  | Up to 82 days post first CYAD-101 Infusion |