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

• ClinicalTrials.gov Identifier: NCT03692429
• Recruitment Status: Recruiting
• First Posted: October 2, 2018
• Last Update Posted: November 20, 2020
• Sponsor: Celyad Oncology SA
• Information provided by (Responsible Party): Celyad Oncology SA

Tracking Information

• First Submitted Date: August 31, 2018
• First Posted Date: October 2, 2018
• Last Update Posted Date: November 20, 2020
• Actual Study Start Date: November 28, 2018
• Estimated Primary Completion Date: November 28, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 19, 2020): Occurence of Dose Limiting Toxicities [ Time Frame: Up to 82 days post first CYAD-101 Infusion ]

Original Primary Outcome Measures (submitted: October 1, 2018)

• Dose Escalation Segment: The occurrence of Dose Limiting Toxicities in all patients during the study treatment until 14 days after the last CYAD-101 study treatment administration (Visit 18). [ Time Frame: During the study treatment until 14 days after the last CYAD-101 study treatment administration (Visit 18 = day 73). ]
  Dose-limiting toxicity refers to a specific adverse event that is experienced during treatment and until 2 weeks after last CYAD-101 dose administration, is new and at least possibly related to CYAD-101 study treatment.
• Expansion Segment: The objective response rate at Visit 18. [ Time Frame: on month 2,5 ]
  The objective response rate at Visit 18 (day 73)

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: October 1, 2018)

• Dose Escalation Segment and Expansion segment: CYAD-101 cell kinetics and dynamics endpoints [ Time Frame: from month 1 till month 2,5 ]
  This endpoint corresponds to the evaluation of the circulating CYAD-101 peripheral blood kinetics post-administration. CYAD-101 detection in peripheral blood-isolated PBMC will be mandatory performed until the end of the administration phase (Visit 18). If positive at Visit 18, the evaluation will be performed during the follow-up period visits and until 2 sequential tests are providing "undetectable" results, suggesting a lack of the CYAD-101 persistence.
• Dose Escalation Segment: Safety endpoints [ Time Frame: from month 1 till month 2,5 ]
  The occurrence of Adverse Events and Serious Adverse Events and Dose Limiting Toxicities during the study treatment until the administration phase concluding visit (Visit 18).
• Dose Escalation and Expansion Segment: Clinical activity endpoints (duration of response) [ Time Frame: up to month 2,4 ]
  The duration of response for patients with objective clinical response.
• Dose Escalation and Expansion Segment: Clinical activity endpoints (occurrence of mixed response) [ Time Frame: up to month 2,4 ]
  The occurrence of mixed response (MR) post CYAD-101 administration.
• Dose Escalation and Expansion Segment: Clinical activity endpoints (progression-free survival) [ Time Frame: up to month 2,4 ]
  The progression-free survival (PFS).
• Dose Escalation and Expansion Segment: Clinical activity endpoints (event-free survival) [ Time Frame: up to month 2,4 ]
  The event-free survival (EFS).
• Dose Escalation and Expansion Segment: Clinical activity endpoints (overall survival) [ Time Frame: up to month 2,4 ]
  The overall survival (OS).
• Expansion Segment: Safety endpoints (occurrence of Dose Limiting Toxicities) [ Time Frame: up to14 days after the last CYAD-101 study treatment administration (month 2,5) ]
  The occurrence of Dose Limiting Toxicities in all patients during the study treatment until 14 days after the last CYAD-101 study treatment administration (Visit 18).
• Expansion Segment: Safety endpoints (occurrence of Adverse Events, Serious Adverse Events and Dose Limiting Toxicities) [ Time Frame: up to 14 days after the last CYAD-101 study treatment administration (month 2,5). ]
  The occurrence of Adverse Events, Serious Adverse Events and Dose Limiting Toxicities during the study treatment until the administration phase concluding visit (Visit 18).
• Mandatory correlative study endpoints (characterization of systemic cytokine level release post CYAD-101) [ Time Frame: up to month 10 ]
  One of the key effector functions of CYAD-101 is the release of soluble cytokines during antigen engagement. Consequently, a surrogate marker of CYAD-101 in vivo activity is potentially raised levels of cytokines relevant to T cell activation within the peripheral circulation.
• Mandatory correlative study endpoints (evaluation of the NKG2D ligand expression within tumor samples prior to treatment administration) [ Time Frame: At screening ]
  The research will evaluate NKG2D ligand expression in patient tumor samples. These are likely to include tumor biopsies but also other sources such as circulating tumor cells where it is possible to isolate sufficient numbers for analysis. The aim of this section is to establish whether a correlation can be drawn between the level of tumor-based NKG2D ligand expression and CYAD-101 activity.
• Mandatory correlative study endpoints (evaluation of biological parameters documenting any Host versus Graft reaction) [ Time Frame: from month 1 up to month 10 ]
  Tumor cell death mediated by CYAD-101 may expose the immune system to new antigens, potentially boosting pre-existing tumor-related immunogenicities or inducing de novo anti-tumor immune responses. Evaluation and characterization of the study treatment mode of action, involving the characterization of the pre-existing and post/during-therapy immune response will be assessed. Moreover, the response of the donor against the allogeneic antigen present on the donor T cells may drive an immunological response clearing the CYAD-101 product. In part, the relative engraftment of CYAD-101 will provide some initial information concerning any potential HvG response (such as reduced persistence of the CYAD-101 cells after second and third infusion). Greater insight into any potential HvG response will be performed within this general immunological assessment of the consequence of CYAD-101 therapy.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: alloSHRINK - Standard cHemotherapy Regimen and Immunotherapy With Allogeneic NKG2D-based CYAD-101 Chimeric Antigen Receptor T-cells
• 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
• 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
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Unresectable Metastatic Colorectal Cancer

Intervention

• Drug: CYAD-101
  Allogeneic NKG2D-based CYAD-101 Chimeric antigen Receptor T-cells
• Drug: FOLFOX
  5-FU, leucovorin and oxaliplatin
• Drug: FOLFIRI
  5-FU, leucovorin and irinotecan

Study Arms

• Experimental: CYAD-101 with FOLFOX
  Infusion after standard FOLFOX chemotherapy
  Interventions:

  • Drug: CYAD-101
  • Drug: FOLFOX
• Experimental: CYAD-101 with FOLFIRI
  Infusion after standard FOLFIRI chemotherapy
  Interventions:

  • Drug: CYAD-101
  • Drug: FOLFIRI

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 19, 2020): 49
• Original Estimated Enrollment (submitted: October 1, 2018): 36
• Estimated Study Completion Date: February 17, 2036
• Estimated Primary Completion Date: November 28, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Histologically proven metastatic adenocarcinoma of the colon or rectum.

   1. Confirmed metastatic unresectable adenocarcinoma of the colon or the rectum.
   2. Recurrent/progressing disease after at least one line of systemic therapy for metastatic disease.
   3. Unequivocal and measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
   4. FOLFOX segment: Neurotoxicity less than or equal to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 from previous chemotherapy.
   5. 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.
2. The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
3. The patient must have adequate bone marrow reserve, hepatic, renal, pulmonary and cardiac functions.

Exclusion Criteria:

1. The patient has a confirmed or history of tumor involvement in the central nervous system (CNS).
2. Any non-cancer-directed investigational agent within 3 weeks before the planned day for the first CYAD-101 administration.
3. Filgrastim (Granulocyte-Colony-Stimulating Factor [G-CSF]) or similar growth factors within 7 days before the planned day for the first CYAD-101 administration.
4. Prior allogeneic stem cell transplantation, chimeric antigen receptor therapy or other genetically modified T-cell therapy.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Celyad Oncology Medical Monitor, MD, PhD; +3210394100; clinicaltrials@celyad.com

• Listed Location Countries: Belgium, United States
• Removed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03692429
• Other Study ID Numbers: CYAD-N2L-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Celyad Oncology SA
• Study Sponsor: Celyad Oncology SA
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Celyad Oncology SA
• Verification Date: November 2020