Relapsed or Refractory Neuroblastoma
Conditions
Keywords
Neuroblastoma, Immunotherapy, 1RG-CART, Cyclophosphamide, Fludarabine, CAR T-cells, Anti-GD2, GD2, CAR, Chimeric Antigen Receptor, Cytokine Release Syndrome
Brief summary
The purpose of this first in human study is to determine the safety and feasibility of 1RG-CART therapy in patients with relapsed or refractory neuroblastoma. 1RG-CART therapy is a novel immunotherapy under investigation in which patients have their T-cells (a type of white blood cell) collected and modified in the laboratory, before they are given back to the patient. The T-cells are modified to express a chimeric antigen receptor (CAR) which targets disialoganglioside (GD2), a marker expressed on the surface of neuroblastoma cells.
Detailed description
The purpose of this trial is to explore the safety and feasibility of deploying autologous anti-GD2 CAR T-cells for the immunotherapy of neuroblastoma. The CAR T-cell trials employing second generation receptors and lymphodepleting conditioning regimes have produced objective clinical responses in patients with relapsed leukaemias. The trial aims to evaluate similar CAR T-cells but directed against the antigen GD2. Neuroblastoma is well suited to this form of targeted therapy because of the homogeneous and almost universal expression of GD2 on the surface of neuroblastoma cells, and because of the poor prognosis of eligible patients. 1RG-CART will be administered intravenously. As the CAR T-cells are designed to survive and proliferate on encountering antigen, no direct relationship is anticipated between cell dose and either efficacy or toxicity. Rather, clinical benefit is more likely to be observed in those patients in whom in vivo expansion successfully occurs. A possible key determinant of expansion will be prior lymphodepletion of the patients. For this reason this trial is designed to evaluate a phased introduction of lymphodepletion in successive patient cohorts, rather than T-cell dose escalation. Only if there is insufficient expansion of T-cells following full lymphodepletion will the T-cell dose be escalated. Rituximab (MabThera®) will be used as a rescue medication only when necessary, and will be considered a non-investigational medicinal product (NIMP) in this trial.
Interventions
OTHERLeukapheresis
DRUGCyclophosphamide
DRUGFludarabine
GENETIC1RG-CART
Sponsors
Cancer Research UK
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligibility Criteria for Leukapheresis/Venepuncture Inclusion Criteria: 1. Written informed consent\* for leukapheresis/venepuncture and transduction of T-cells. 2. Suitability for leukapheresis/venepuncture defined as: * Negative for human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV) 1, HTLV 2, syphilis and hepatitis B. * Minimum T-lymphocyte count of 0.25x10\^9/L. 3. Relapsed or refractory neuroblastoma (the patient must have evidence of active disease even if they do not currently require active treatment). 4. Patients must have at least one lesion that can be evaluated for response by imaging and/or diffuse bone marrow infiltration. 5. Adequate renal function, defined as a glomerular filtration rate (GFR) ≥ 30 mL/min/1.73m\^2 (corrected). 6. Karnofsky score ≥60% if ≥16 years old or Lansky performance score of ≥60% if \<16 years old * \*Informed consent from the patient's parent or legal guardian is required for all patients under 16 years of age. Patients under 16 years of age may also provide written assent to take part in the trial.
Exclusion criteria
Patients should not meet (or be anticipated to meet) any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Day 14 | Feasibility of 1RG-CART therapy assessed as the number of patients who commence T-cell processing and are subsequently evaluable for 1RG-CART engraftment at Day 14. |
| Safety and Tolerability of 1RG-CART Therapy | From the time of informed consent to leukapheresis until withdrawal from the trial or start of other anti-cancer therapy (a median time period of 132 days [range 68 to 301 days]) | Number of serious adverse events, non-serious adverse events and adverse events that are related to fludarabine, cyclophosphamide or 1RG-CART. |
| To Determine Recommended Phase II Regimen by Assessing the Number of DLTs at Each Dose Level | From the time of informed consent to leukapheresis until withdrawal from the trial or start of other anti-cancer therapy (a median time period of 132 days [range 68 to 301 days]) | Number of dose limiting toxicities (DLTs) at each dose level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Tumour Response From Baseline (INRC) | Day 28, 2 months and 4 months | Assessment of best tumour response from baseline according to International Neuroblastoma Response Criteria (INRC). |
| 1RG-CART Counts in the Peripheral Blood | From Day 0 until end of trial (median 38.5 days, range 20 to 233 days) | Number of patients with 1RG-CART levels in peripheral blood above the limit of quantification for the assay (10 cells/µL) by flow cytometry. |
| To Evaluate Anti-tumour Activity (Overall Survival) | Up to 2 years | Overall survival. |
| To Evaluate Anti-tumour Activity (Progression Free Survival) | Up to 2 years | Progression free survival (progression by RECIST criteria). |
| Assessment of Tumour Response From Baseline (RECIST) | Day 28, 2 months and 4 months | Assessment of best tumour response from baseline according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. |
| Assessment of Tumour Response From Baseline (irRC) | Day 28, 2 months and 4 months | Assessment of best tumour response from baseline according to Immune Related Response Criteria (irRC). |
Countries
United Kingdom
Participant flow
Recruitment details
17 trial participants were enrolled at one trial site between 29 February 2016 and 19 November 2019.
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 1 Patients in Dose Level 1 will receive 1x10\^7 1RG-CART/m\^2 IV on Day 0.
Assigned Interventions:
Leukapheresis
1RG-CART | 4 |
| Dose Level 2 Patients in Dose Level 2 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -4 to -1) followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.
Assigned Interventions:
Leukapheresis
Cyclophosphamide
1RG-CART | 1 |
| Dose Level 3 Patients in Dose Level 3 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.
Assigned Interventions:
Cyclophosphamide
Fludarabine
Leukapheresis
1RG-CART | 1 |
| Dose Level 4 Patients in Dose Level 4 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^8 1RG-CART/m\^2 IV on Day 0.
Assigned Interventions:
Cyclophosphamide
Fludarabine
Leukapheresis
1RG-CART | 3 |
| Dose Level 5 If the required level of 1RG-CART survival is not reached, a further cohort of patients (Dose Level 5) will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 5-10x10\^8 1RG-CART/m\^2 IV which could be be split over two days (Day 0 and Day 1).
Assigned Interventions:
Cyclophosphamide
Fludarabine
Leukapheresis
1RG-CART | 3 |
| Patients Who Underwent Leukapheresis But Did Not Proceed to Receive Any IMP Patients who were enrolled and underwent leukapheresis but who did not receive any IMP.
Assigned Interventions:
Leukapheresis | 5 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 1 | 1 | 1 | 0 | 1 |
| Overall Study | Disease Progression | 0 | 0 | 0 | 2 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Dose Level 2 | Dose Level 3 | Dose Level 4 | Dose Level 5 | Dose Level 1 | Patients Who Underwent Leukapheresis But Did Not Proceed to Receive Any IMP |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 17 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 4 Participants | 5 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — | — | — | — |
| Region of Enrollment United Kingdom | 17 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Female | 6 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 11 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 1 / 1 | 1 / 1 | 1 / 3 | 0 / 3 |
| other Total, other adverse events | 4 / 4 | 1 / 1 | 1 / 1 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 0 / 4 | 0 / 1 | 0 / 1 | 2 / 3 | 3 / 3 |
Outcome results
Primary
Safety and Tolerability of 1RG-CART Therapy
Number of serious adverse events, non-serious adverse events and adverse events that are related to fludarabine, cyclophosphamide or 1RG-CART.
Time frame: From the time of informed consent to leukapheresis until withdrawal from the trial or start of other anti-cancer therapy (a median time period of 132 days [range 68 to 301 days])
Population: All eligible patients who received at least one dose of 1RG-CART, cyclophosphamide or fludarabine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Level 1 | Safety and Tolerability of 1RG-CART Therapy | Cyclophosphamide Related AEs | NA Events |
| Dose Level 1 | Safety and Tolerability of 1RG-CART Therapy | SAEs | 0 Events |
| Dose Level 1 | Safety and Tolerability of 1RG-CART Therapy | 1RG-CART Related AEs | 4 Events |
| Dose Level 1 | Safety and Tolerability of 1RG-CART Therapy | NSAEs | 31 Events |
| Dose Level 1 | Safety and Tolerability of 1RG-CART Therapy | Fludarabine Related AEs | NA Events |
| Dose Level 2 | Safety and Tolerability of 1RG-CART Therapy | Cyclophosphamide Related AEs | 8 Events |
| Dose Level 2 | Safety and Tolerability of 1RG-CART Therapy | Fludarabine Related AEs | NA Events |
| Dose Level 2 | Safety and Tolerability of 1RG-CART Therapy | NSAEs | 13 Events |
| Dose Level 2 | Safety and Tolerability of 1RG-CART Therapy | 1RG-CART Related AEs | 2 Events |
| Dose Level 2 | Safety and Tolerability of 1RG-CART Therapy | SAEs | 0 Events |
| Dose Level 3 | Safety and Tolerability of 1RG-CART Therapy | Fludarabine Related AEs | 7 Events |
| Dose Level 3 | Safety and Tolerability of 1RG-CART Therapy | SAEs | 0 Events |
| Dose Level 3 | Safety and Tolerability of 1RG-CART Therapy | NSAEs | 15 Events |
| Dose Level 3 | Safety and Tolerability of 1RG-CART Therapy | Cyclophosphamide Related AEs | 7 Events |
| Dose Level 3 | Safety and Tolerability of 1RG-CART Therapy | 1RG-CART Related AEs | 0 Events |
| Dose Level 4 | Safety and Tolerability of 1RG-CART Therapy | 1RG-CART Related AEs | 25 Events |
| Dose Level 4 | Safety and Tolerability of 1RG-CART Therapy | SAEs | 5 Events |
| Dose Level 4 | Safety and Tolerability of 1RG-CART Therapy | Cyclophosphamide Related AEs | 18 Events |
| Dose Level 4 | Safety and Tolerability of 1RG-CART Therapy | Fludarabine Related AEs | 18 Events |
| Dose Level 4 | Safety and Tolerability of 1RG-CART Therapy | NSAEs | 75 Events |
| Dose Level 5 | Safety and Tolerability of 1RG-CART Therapy | Fludarabine Related AEs | 25 Events |
| Dose Level 5 | Safety and Tolerability of 1RG-CART Therapy | Cyclophosphamide Related AEs | 27 Events |
| Dose Level 5 | Safety and Tolerability of 1RG-CART Therapy | SAEs | 7 Events |
| Dose Level 5 | Safety and Tolerability of 1RG-CART Therapy | 1RG-CART Related AEs | 33 Events |
| Dose Level 5 | Safety and Tolerability of 1RG-CART Therapy | NSAEs | 86 Events |
Primary
To Determine Recommended Phase II Regimen by Assessing the Number of DLTs at Each Dose Level
Number of dose limiting toxicities (DLTs) at each dose level.
Time frame: From the time of informed consent to leukapheresis until withdrawal from the trial or start of other anti-cancer therapy (a median time period of 132 days [range 68 to 301 days])
Population: All eligible patients who received at least one dose of 1RG-CART, cyclophosphamide or fludarabine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Level 1 | To Determine Recommended Phase II Regimen by Assessing the Number of DLTs at Each Dose Level | 0 DLT events |
| Dose Level 2 | To Determine Recommended Phase II Regimen by Assessing the Number of DLTs at Each Dose Level | 0 DLT events |
| Dose Level 3 | To Determine Recommended Phase II Regimen by Assessing the Number of DLTs at Each Dose Level | 0 DLT events |
| Dose Level 4 | To Determine Recommended Phase II Regimen by Assessing the Number of DLTs at Each Dose Level | 0 DLT events |
| Dose Level 5 | To Determine Recommended Phase II Regimen by Assessing the Number of DLTs at Each Dose Level | 0 DLT events |
Primary
To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma
Feasibility of 1RG-CART therapy assessed as the number of patients who commence T-cell processing and are subsequently evaluable for 1RG-CART engraftment at Day 14.
Time frame: Day 14
Population: All eligible patients enrolled for leukapheresis/venepuncture. Patients who were enrolled for leukapheresis/venepuncture in error (due to ineligibility or administrative error) were excluded.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level 1 | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis only | 0 Participants |
| Dose Level 1 | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis and received 1RG-CART | 4 Participants |
| Dose Level 2 | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis only | 0 Participants |
| Dose Level 2 | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis and received 1RG-CART | 1 Participants |
| Dose Level 3 | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis only | 0 Participants |
| Dose Level 3 | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis and received 1RG-CART | 1 Participants |
| Dose Level 4 | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis only | 0 Participants |
| Dose Level 4 | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis and received 1RG-CART | 3 Participants |
| Dose Level 5 | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis only | 0 Participants |
| Dose Level 5 | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis and received 1RG-CART | 3 Participants |
| Patients Who Underwent Leukapheresis But Did Not Proceed to Receive Any IMP | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis only | 5 Participants |
| Patients Who Underwent Leukapheresis But Did Not Proceed to Receive Any IMP | To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma | Underwent Leukapheresis and received 1RG-CART | 0 Participants |
Secondary
1RG-CART Counts in the Peripheral Blood
Number of patients with 1RG-CART levels in peripheral blood above the limit of quantification for the assay (10 cells/µL) by flow cytometry.
Time frame: From Day 0 until end of trial (median 38.5 days, range 20 to 233 days)
Population: All eligible patients who received 1RG-CART and provided at least one post-treatment blood sample taken on or after Day 14 for 1RG-CART analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Level 1 | 1RG-CART Counts in the Peripheral Blood | 0 Participants |
| Dose Level 2 | 1RG-CART Counts in the Peripheral Blood | 0 Participants |
| Dose Level 3 | 1RG-CART Counts in the Peripheral Blood | 0 Participants |
| Dose Level 4 | 1RG-CART Counts in the Peripheral Blood | 0 Participants |
| Dose Level 5 | 1RG-CART Counts in the Peripheral Blood | 1 Participants |
Secondary
Assessment of Tumour Response From Baseline (INRC)
Assessment of best tumour response from baseline according to International Neuroblastoma Response Criteria (INRC).
Time frame: Day 28, 2 months and 4 months
Population: All eligible patients who received at least one dose of 1RG-CART and had a baseline assessment of disease and at least one repeat disease assessment measured according to International Neuroblastoma Response Criteria (INRC).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level 1 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) Mixed response | 0 Participants |
| Dose Level 1 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) Progressive disease | 1 Participants |
| Dose Level 1 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) No response | 2 Participants |
| Dose Level 2 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) No response | 0 Participants |
| Dose Level 2 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) Mixed response | 0 Participants |
| Dose Level 2 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) Progressive disease | 1 Participants |
| Dose Level 3 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) No response | 1 Participants |
| Dose Level 3 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) Mixed response | 0 Participants |
| Dose Level 3 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) Progressive disease | 0 Participants |
| Dose Level 4 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) Mixed response | 1 Participants |
| Dose Level 4 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) Progressive disease | 1 Participants |
| Dose Level 4 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) No response | 0 Participants |
| Dose Level 5 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) No response | 0 Participants |
| Dose Level 5 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) Mixed response | 0 Participants |
| Dose Level 5 | Assessment of Tumour Response From Baseline (INRC) | Best Response (INRC) Progressive disease | 3 Participants |
Secondary
Assessment of Tumour Response From Baseline (irRC)
Assessment of best tumour response from baseline according to Immune Related Response Criteria (irRC).
Time frame: Day 28, 2 months and 4 months
Population: All eligible patients who received at least one dose of 1RG-CART and had a baseline assessment of disease and at least one repeat disease assessment measured according to Immune Related Response Criteria (irRC).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level 1 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) stable disease (irSD) | 2 Participants |
| Dose Level 1 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) not evaluable (NE) | 0 Participants |
| Dose Level 1 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) progressive disease (irPD) | 1 Participants |
| Dose Level 2 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) progressive disease (irPD) | 1 Participants |
| Dose Level 2 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) stable disease (irSD) | 0 Participants |
| Dose Level 2 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) not evaluable (NE) | 0 Participants |
| Dose Level 3 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) progressive disease (irPD) | 0 Participants |
| Dose Level 3 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) stable disease (irSD) | 1 Participants |
| Dose Level 3 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) not evaluable (NE) | 0 Participants |
| Dose Level 4 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) stable disease (irSD) | 1 Participants |
| Dose Level 4 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) not evaluable (NE) | 1 Participants |
| Dose Level 4 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) progressive disease (irPD) | 0 Participants |
| Dose Level 5 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) progressive disease (irPD) | 1 Participants |
| Dose Level 5 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) stable disease (irSD) | 1 Participants |
| Dose Level 5 | Assessment of Tumour Response From Baseline (irRC) | Best Response (irRC) not evaluable (NE) | 1 Participants |
Secondary
Assessment of Tumour Response From Baseline (RECIST)
Assessment of best tumour response from baseline according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.
Time frame: Day 28, 2 months and 4 months
Population: All eligible patients who received at least one dose of 1RG-CART and had a baseline assessment of disease and at least one repeat disease assessment measured according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Level 1 | Assessment of Tumour Response From Baseline (RECIST) | Best Response (RECIST) stable disease (SD) | 2 Participants |
| Dose Level 1 | Assessment of Tumour Response From Baseline (RECIST) | Best Response (RECIST) progressive disease (PD) | 1 Participants |
| Dose Level 2 | Assessment of Tumour Response From Baseline (RECIST) | Best Response (RECIST) stable disease (SD) | 0 Participants |
| Dose Level 2 | Assessment of Tumour Response From Baseline (RECIST) | Best Response (RECIST) progressive disease (PD) | 1 Participants |
| Dose Level 3 | Assessment of Tumour Response From Baseline (RECIST) | Best Response (RECIST) stable disease (SD) | 1 Participants |
| Dose Level 3 | Assessment of Tumour Response From Baseline (RECIST) | Best Response (RECIST) progressive disease (PD) | 0 Participants |
| Dose Level 4 | Assessment of Tumour Response From Baseline (RECIST) | Best Response (RECIST) progressive disease (PD) | 1 Participants |
| Dose Level 4 | Assessment of Tumour Response From Baseline (RECIST) | Best Response (RECIST) stable disease (SD) | 1 Participants |
| Dose Level 5 | Assessment of Tumour Response From Baseline (RECIST) | Best Response (RECIST) stable disease (SD) | 1 Participants |
| Dose Level 5 | Assessment of Tumour Response From Baseline (RECIST) | Best Response (RECIST) progressive disease (PD) | 2 Participants |
Secondary
To Evaluate Anti-tumour Activity (Overall Survival)
Overall survival.
Time frame: Up to 2 years
Population: Patients who received 1RG-CART.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Level 1 | To Evaluate Anti-tumour Activity (Overall Survival) | 170 Days |
| Dose Level 2 | To Evaluate Anti-tumour Activity (Overall Survival) | 261 Days |
| Dose Level 3 | To Evaluate Anti-tumour Activity (Overall Survival) | 113 Days |
| Dose Level 4 | To Evaluate Anti-tumour Activity (Overall Survival) | 60 Days |
| Dose Level 5 | To Evaluate Anti-tumour Activity (Overall Survival) | NA Days |
Secondary
To Evaluate Anti-tumour Activity (Progression Free Survival)
Progression free survival (progression by RECIST criteria).
Time frame: Up to 2 years
Population: All eligible patients who received 1RG-CART and completed a baseline assessment of disease and at least one repeat disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Level 1 | To Evaluate Anti-tumour Activity (Progression Free Survival) | 122 Days |
| Dose Level 2 | To Evaluate Anti-tumour Activity (Progression Free Survival) | 34 Days |
| Dose Level 3 | To Evaluate Anti-tumour Activity (Progression Free Survival) | 113 Days |
| Dose Level 4 | To Evaluate Anti-tumour Activity (Progression Free Survival) | 39.5 Days |
| Dose Level 5 | To Evaluate Anti-tumour Activity (Progression Free Survival) | 27 Days |