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Haplo / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted γδ T Cells for Relapsed or Refractory Solid Tumour

Primary Purpose

Colorectal Cancer, Triple Negative Breast Cancer, Sarcoma

Status

Unknown status

Phase

Phase 1

Locations

Malaysia

Study Type

Interventional

Intervention

Adoptive Cell Transfer of NKG2DL-targetting Chimeric Antigen Receptor-grafted Gamma Delta T cell

About this trial

This is an interventional other trial for Colorectal Cancer focused on measuring NKG2D, gamma, delta, T cell, CAR, chimeric antigen receptor, solid tumour, cancer immunotherapy, adoptive cell transfer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Men or women ≥18 years old.
Patient with specific cancer indications (see below).
Disease must be measurable according to the corresponding guidelines.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or 2.
Patient with adequate bone marrow reserve (Haemoglobin ≥10g/dl, Absolute Neutrophil Count (ANC)≥1,500/mm3, Platelet≥100,000/mm3), hepatic function (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 3x upper limit of normal), renal function (serum creatinine < 120 µmol/L) and cardiac function (Left ventricular ejection fraction of ≥50% by ECHO).
Patient must already have a previous tumour biopsy to confirm the disease.
Patient must agree to sign the informed consent form (ICF).

Cancer-specific inclusion criteria of subject:

Colorectal cancer: A documented metastatic colorectal adenocarcinoma and having received, being intolerant to or being unfit for at least two prior standard cancer therapy regimens as part of their primary treatment regimen or part of their treatment for management of recurrent/persistent disease.
Breast cancer: A metastatic triple-negative breast cancer and having received at least two prior cancer therapy regimens as part of their treatment for management of recurrent/persistent disease.
Sarcoma, nasopharyngeal cancer, prostate cancer or gastric cancer: A metastatic cancer and having received at least two prior cancer therapy regimens as part of their treatment for management of recurrent/persistent disease.

Exclusion Criteria:

Patients with a tumour metastasis in the central nervous system.
Patients who receive or are to receive any investigational product within the 4 weeks before the planned day for the first CTM-N2D administration.
Patients who receive or are to receive chemotherapy within the 8 weeks before the planned day for the first CTM-N2D administration.
Patients who are planned to receive concurrent growth factor, systemic steroid or other immunosuppressive therapy or cytotoxic agent.
Patients who underwent major surgery within 4 weeks before the planned day for the first CTM-N2D administration.
Patients who have active infections necessitating the use of antibiotics/antivirals treatment.
Patients with a history of autoimmune disease.

Sites / Locations

Landmark Medical Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR-T Cell Therapy Group

Arm Description

One arm study consisting of "3 + 3" dose escalation study design ranging from 3 x 10^8 - 3 x 10^9 cells CAR-γδ T cell. Each cycle of therapy will consist of 4 intravenous infusions, given 7 days apart.

Outcomes

Primary Outcome Measures

Number of Patients with Dose Limiting Toxicity

The primary endpoint of this dose-escalation study will be the occurrence of dose-limiting toxicities (DLTs) during 4 cycles of treatment and the week after treatment.

Secondary Outcome Measures

Occurence of adverse events during therapy

A secondary outcome is to observe for the occurence of any adverse events (AEs) and serious adverse events (SAEs) during 4 cycles of treatment and the week after treatment

Observation of clinical efficacy

A secondary outcome is to observe for the occurrence of objective clinical response at d31, M3, M6, M9, M12, M18 and M24 after the start of 1st cycle of treatment (assessed according to RECIST criteria, version 1.1)

Observation for progression-free survival

A secondary outcome is to observe for progression-free survival (PFS) and after the start of 1st cycle of treatment

Observation for duration of response

A secondary outcome is to observe the duration of response in patients with objective response up to M24, After the start of 1st cycle of treatment

Full Information

NCT ID

NCT04107142

First Posted

September 21, 2019

Last Updated

September 26, 2019

Sponsor

CytoMed Therapeutics Pte Ltd

1. Study Identification

Unique Protocol Identification Number

NCT04107142

Brief Title

Haplo / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted γδ T Cells for Relapsed or Refractory Solid Tumour

Official Title

A Phase I Dose-escalation Trial to Evaluate Haploidentical / Allogeneic Natural Killer Group 2D Ligand (NKG2DL)-Targeting Chimeric Antigen Receptor-grafted Gamma Delta (γδ) T Cells (CTM-N2D) in Subjects With Relapsed or Refractory Solid Tumour

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Unknown status

Study Start Date

December 1, 2019 (Anticipated)

Primary Completion Date

September 1, 2020 (Anticipated)

Study Completion Date

March 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

CytoMed Therapeutics Pte Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This clinical trial is an open-label, single-centre, dose escalation, phase I study designed to investigate the safety and tolerability of Haploidentical / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted Gamma Delta (γδ) T Cells (CTM-N2D) in Subjects with Relapsed or Refractory Solid Tumour. The study objectives of this phase I study are to determine the safety, activity and the safe dose of haploidentical or allogeneic NKG2DL-targeting chimeric antigen receptor-grafted γδ T cells given four times weekly in patients with relapsed or refractory solid tumors of different types.

Detailed Description

CTM-N2D-101 is a phase I dose-escalation study to evaluate the safety of CTM-N2D and the feasibility to produce CTM-N2D for three target dose levels between 3x10^8 - 3x10^9 per infusion will be tested. Four doses will be given at an interval of a week into subjects with relapsed or refractory solid tumors. A typical 3+3 design will be used to determine the safe regimen basing on the incidence of dose-limiting toxicity (DLT). The identified safe regimen will be used for further phase II studies for selected indications.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer, Triple Negative Breast Cancer, Sarcoma, Nasopharyngeal Carcinoma, Prostate Cancer, Gastric Cancer

Keywords

NKG2D, gamma, delta, T cell, CAR, chimeric antigen receptor, solid tumour, cancer immunotherapy, adoptive cell transfer

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

The study consisT of "3 + 3" dose escalation study design with 3 distinct dose level. The first dose level will be at 3 x 10^8 chimeric antigen receptor (CAR) grafted γδ T cells per infusion. The second dose level will be at 1 x 10^9 CAR-γδT cells per infusion. The third dose level will be increased to 3 x 10^9 cells CAR-γδT cells. Each cycle of therapy will consist of 4 intravenous infusions, given 7 days apart.

Masking

None (Open Label)

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CAR-T Cell Therapy Group

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Adoptive Cell Transfer of NKG2DL-targetting Chimeric Antigen Receptor-grafted Gamma Delta T cell

Intervention Description

Adoptive Cell Transfer of Haploidentical / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted γδ T Cells (CTM-N2D)

Primary Outcome Measure Information:

Title

Number of Patients with Dose Limiting Toxicity

Description

The primary endpoint of this dose-escalation study will be the occurrence of dose-limiting toxicities (DLTs) during 4 cycles of treatment and the week after treatment.

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Occurence of adverse events during therapy

Description

A secondary outcome is to observe for the occurence of any adverse events (AEs) and serious adverse events (SAEs) during 4 cycles of treatment and the week after treatment

Time Frame

6 months

Title

Observation of clinical efficacy

Description

Time Frame

6 months to 2 years

Title

Observation for progression-free survival

Description

A secondary outcome is to observe for progression-free survival (PFS) and after the start of 1st cycle of treatment

Time Frame

up to 2 years

Title

Observation for duration of response

Description

A secondary outcome is to observe the duration of response in patients with objective response up to M24, After the start of 1st cycle of treatment

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men or women ≥18 years old. Patient with specific cancer indications (see below). Disease must be measurable according to the corresponding guidelines. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or 2. Patient with adequate bone marrow reserve (Haemoglobin ≥10g/dl, Absolute Neutrophil Count (ANC)≥1,500/mm3, Platelet≥100,000/mm3), hepatic function (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 3x upper limit of normal), renal function (serum creatinine < 120 µmol/L) and cardiac function (Left ventricular ejection fraction of ≥50% by ECHO). Patient must already have a previous tumour biopsy to confirm the disease. Patient must agree to sign the informed consent form (ICF). Cancer-specific inclusion criteria of subject: Colorectal cancer: A documented metastatic colorectal adenocarcinoma and having received, being intolerant to or being unfit for at least two prior standard cancer therapy regimens as part of their primary treatment regimen or part of their treatment for management of recurrent/persistent disease. Breast cancer: A metastatic triple-negative breast cancer and having received at least two prior cancer therapy regimens as part of their treatment for management of recurrent/persistent disease. Sarcoma, nasopharyngeal cancer, prostate cancer or gastric cancer: A metastatic cancer and having received at least two prior cancer therapy regimens as part of their treatment for management of recurrent/persistent disease. Exclusion Criteria: Patients with a tumour metastasis in the central nervous system. Patients who receive or are to receive any investigational product within the 4 weeks before the planned day for the first CTM-N2D administration. Patients who receive or are to receive chemotherapy within the 8 weeks before the planned day for the first CTM-N2D administration. Patients who are planned to receive concurrent growth factor, systemic steroid or other immunosuppressive therapy or cytotoxic agent. Patients who underwent major surgery within 4 weeks before the planned day for the first CTM-N2D administration. Patients who have active infections necessitating the use of antibiotics/antivirals treatment. Patients with a history of autoimmune disease.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Peter Choo

Phone

+65 9732 8844

peterchoo@cytomed.sg

First Name & Middle Initial & Last Name or Official Title & Degree

Wee Kiat Tan

Phone

+65 9816 9085

weekiattan@cytomed.sg

Facility Information:

Facility Name

Landmark Medical Centre

City

Johor Bahru

State/Province

Johor

ZIP/Postal Code

80000

Country

Malaysia

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lucas Luk

drlucas@landmarkmedical.com.my

First Name & Middle Initial & Last Name & Degree

Wee Kiat Tan

weekiattan@cytomed.sg

First Name & Middle Initial & Last Name & Degree

Lucas Luk

12. IPD Sharing Statement

Plan to Share IPD

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Haplo / Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted γδ T Cells for Relapsed or Refractory Solid Tumour

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