About the study

This open-label Phase I study aims at assessing the safety, cell kinetics and clinical activity of the CYAD-101 treatment administered 3 times with a 2-week interval between each administration in metastatic colorectal cancer, concurrently with a standard chemotherapy treatment. The standard chemotherapy treatment consists in 6 consecutive cycles of FOLFOX, administered with a 2-week interval. The CYAD-101 treatment will be administered at a specific time point within the third, fourth and fifth chemotherapy cycles. This Phase I study will contain two consecutive segments: a dose-escalation and an expansion segment: The first segment (dose-escalation segment) will use a 3+3 design to determine the recommended dose of CYAD-101 on the basis of dose-limiting toxicities (DLTs). The second segment (expansion segment) of the study will evaluate 3 injections of CYAD-101 at the recommended dose defined in the first segment, administered concurrently with FOLFOX, in a larger number of patients.

Who can take part?

You may be eligible to participate in the study if you meet the following criteria:

Inclusion criteria

1. The patient must have signed the written ICF and must accept to be monitored for up to 15 years in a Long-Term Safety Follow-Up (LTSFU) protocol.
2. Both men and women of all races and ethnic groups are eligible.
3. The patient must be < = 18 years old at the time of signing the ICF.
4. The patient must have a histologically proven metastatic adenocarcinoma of the colon or rectum.
5. Unresectable metastases not treatable by surgical resection or local ablation with curative intent at time of study entry.
6. Unequivocal and measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
7. The patient is due to receive first-line metastatic chemotherapy regimen with FOLFOX, as permitted in this protocol. Notes: Patients who have received adjuvant chemotherapy or chemoradiotherapy to the pelvis, provided the last dose of chemotherapy was administered at least 6 months prior to the first CYAD-101 administration, are permitted.
8. The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
9. The patient must have the bone marrow reserve, hepatic and renal functions described with LLN/ULN being the lower/upper limit of normal, respectively:
10. Hemoglobin > 9.0 g/dl
11. ANC > 800/µL
12. Platelet count >= 80000/µL
13. LDH <= 1.5 x ULN
14. Serum creatinine <= 2.0 mg/dl
15. Total serum bilirubin <= 1.75 mg/dL
16. ALT <= 5 x ULN
17. AST <= 5 x ULN
18. The patient must agree to have a tumor biopsy at baseline. In specific cases, where tumor biopsy is not possible, decision to not perform the tumor biopsy may be taken by the Investigator but only after approval from the Sponsor.
19. Ejection fraction of > 40%, as determined by echocardiography or a multigated acquisition (MUGA) scan.
20. Women of child-bearing potential and men must agree to use effective contraception before, during and for at least 2 months after the last study treatment administration. Notes: Adequate contraception is defined as methods of birth control that, alone or in combination, result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly. These include established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; male sterilization, true abstinence (when this is in line with the preferred and usual lifestyle of the patient). Women of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as the consequence of hysterectomy, ovariectomy or post-menopause.
21. The patient must, in the opinion of the Investigator, be able to adhere with the study visit schedule and all study procedures described in this protocol.

Exclusion criteria

1. The patient has a confirmed or suspected tumor metastasis in the central nervous system (CNS). A neurological examination is to be performed systematically at baseline. In case signs or symptoms suggestive of potential CNS disease are observed, CNS imaging is to be performed. Peripheral neuropathy from prior therapy is acceptable.
2. Patients who have received any cancer therapy (investigational agent or not), including but not limited to chemotherapy, small molecules, monoclonal antibodies (e.g., immune checkpoint blockade therapies), or radiotherapy within 2 weeks before the planned D1. Note: Per study design the standard FOLFOX chemotherapy is authorized.
3. Patients who are planned to receive or concurrently receiving any other non-cancer-directed investigational agent or have received another non-cancer-directed investigational agent within 3 weeks before the planned day for the first CYAD-101 administration.
4. Patient is under systemic immunosuppressive drugs, unless specific cases authorized per protocol (see Section 6.5).
5. Patients who have received prior allogeneic stem cell transplantation, chimeric antigen receptor therapy or other genetically modified T-cell therapy.
6. Patients who are presenting persistent toxicities greater than or equal to CTCAE grade 2 caused by previous adjuvant cancer therapy (except for clinically non-significant toxicities, such as alopecia).
7. Presence of any indwelling catheter or drain (e.g., percutaneous nephrostomy tube, indwelling foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter) may be permissive unless they have a catheter-associated infection that cannot be cleared with antibiotics. Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath, peripherally inserted central catheter, or Hickman catheter are permitted.
8. Patients who underwent major surgery within 4 weeks before the planned day for the first CYAD-101 administration. Note: Placement of vascular access device or tumor biopsies are authorized until 10 days before the planned day for the first CYAD-101 administration.
9. Patients who have received a live vaccine within 6 weeks prior to the planned day for the first CYAD-101 administration.
10. Patients with uncontrolled intercurrent illness or serious uncontrolled medical disorder including, but not limited to evidence of active pneumonitis on screening chest imaging, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia and/or pronounced disturbances of the electrical conduction system of the heart, or significant thromboembolic events.
11. Patient with history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, and/or active or acute exacerbation of chronic obstructive pulmonary disease (COPD). Note: Patients with history or suspicion of COPD must have at least Forced Expiratory Volume in the first second (FEV-1)/ Forced Vital Capacity (FVC) >= 0,7 with FEV-1 >= 50% predicted (GOLD 1 or 2 severity).
12. Patients who have active infections necessitating use of antibiotics/antivirals treatment (prophylaxis is acceptable).
13. Patients with significant disorder of coagulation or receiving treatment with warfarin derivatives or heparin. Note: Patients receiving systemic individual doses of low molecular weight heparin outside 24 hours prior to each CYAD-101 administration are eligible.
14. Patients who are known to be positive or screened positive for the human immunodeficiency virus (HIV).
15. Patients with a family history of congenital or hereditary immunodeficiency.
16. Patients with a history of allergic reactions or hypersensitivity attributed to Human serum albumin or Plasma-lyte A.
17. Patients on supplemental home oxygen.
18. Patients with history of any autoimmune disease including, but not limited to inflammatory bowel disease (including ulcerative colitis and Crohn's Disease), systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g., Wegener's granulomatosis), CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis). Patients with Graves disease and vitiligo will be allowed.
19. Patients with a history of a malignancy other than the one evaluated in this study enrollment, with exception of the following circumstances:
20. Patients with a history of malignancy who have been adequately treated and have been disease-free for at least 1 year, and
21. Patients with adequately treated active non-invasive cancers (such as non-melanomatous skin cancer or in-situ bladder, cervical and breast cancers).
22. Patients with psychiatric/social situations or addictive disorders that may compromise the ability of the patients to give informed consent or to comply with the study procedures
23. Female patients who are pregnant or lactating.

For a full list of inclusion/exclusion criteria, please visit ClinicalTrials.gov

Study locations

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How to apply

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