Stage IV colorectal cancer. MedDRA version: 21.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: pTTL
Pharmaceutical Form: Infusion
INN or Proposed INN: Not assigned
Current Sponsor code: pTTL (personalised tumour-trained lymphocytes)
Concentration unit: U/ml unit(s)/millilitre
Conc
Sponsors
NEOGAP Therapeutics AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Applicable for both Part I and Part 2: 1. Signed informed consent. 2. Adult (age =18 years). 3. Histological or cytological confirmation of colorectal cancer. 4. Verified metastatic disease (stage IV classification). 5. Measurable disease according to RECIST1.1. 6 (no 7 in part 2). Minimum life expectancy of 6 months (part I) or 3 months (part II). 7 (no 8 in part 2). ECOG performance status 0 to 1 8 (no 9 in part 2). Adequate bone marrow, hepatic and renal function defined as: a. Haemoglobin = 95 g/L (blood transfusion not less than 21 days prior to screening), b. Absolute neutrophil count = 1.0 x 109/L, platelets =100 x 109/L c. Total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: 1.Less than 4 months (Part 1) or 6 months (Part 2) since a clinically significant cardiovascular event such as myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke or transient ischemic attack (TIA). Atrial fibrillation if treated and well controlled is not considered a bar to inclusion even if diagnosed less than 6 months ago 2.(Applicable for Part 1) For patients scheduled for trial specific surgery:Left ventricular ejection fraction (LVEF) <45% and/or significant heart valve dysfunction (stenosis or insufficiency) as determined by echocardiogram performed within 3 months of the screening visit (Visit 1).For patients scheduled for standard surgery:congestive heart failure New York Heart Association (NYHA) class III or IV.Echocardiogram for inclusion in Part I is not mandatory due to time limitations prior to standard surgery 2.(Applicable for Part 2) LVEF <45% and/or significant heart valve dysfunction (stenosis or insufficiency) as determined by echocardiogram performed within 3 month before start of pre conditioning therapy,or more recently if clinically indicated 3.Significantly reduced lung function with clinical implications.If such is suspected, spirometry should be performed.Spirometry should also be considered in patients who have been hospitalised due to Covid-19 infection during the last 6 months, and in patients with any other lung affectation judged significant by the Investigators, in discussion with Sponsor’s Medical Representative,such as treatment-related pneumonitis or severe lung infection.Spirometry results of less than 65% of the expected value regarding forced expiratory volume in 1 second (FEV1) and/or diffusion capacity (diffusing capacity of the lung for carbon monoxide, DLCO, corrected for haemoglobin value, DLCOco) is regarded as a criterium for exclusion For patients scheduled for standard surgery:not applicable - spirometry for inclusion in Part I is not mandatory due to time limitations prior to standard surgery 4.Any severe acute or chronic medical condition that places the patient at increased risk or interferes with the interpretation of trial results (as judged by the Investigators, in agreement with Sponsor’s Medical Representative) 5.Immunodeficiency disorders which may pose a risk for patients treated with pTTL, and/or affect the outcome of the pTTL treatment as judged by the Investigator at the Recruitment, Surgery & Treatment Site. 6.Autoimmunity disorders which may pose a risk for patients treated with pTTL, and/or affect the outcome of the pTTL treatment,as judged by the Investigator at the Recruitment, Surgery & Treatment Site 7.Leptomeningeal metastases (patient with previously treated brain metastases are eligible if there is no evidence of disease progression for a minimum of 8 weeks prior to inclusion – in these cases a CNS MRI is required within the screening period.These patients must not have symptoms from their brain metastases or treatment thereof and must not be taking steroid medications for treatment of CNS symptoms) 8. Systemic immunosuppressive concomitant medications,including chemotherapy for CRC and steroids for antiemetic prophylaxis, must be discountinued at a minimum 2 weeks prior to surgery.Steroid medications are allowed if they are used as substitution or are administrated topically or as inhalation steroids for asthma 9.Previous Grade 3 or greater immune-related toxicity from checkpoint modulation or other immunotherapy (unless the toxicity has re
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish that pTTL can be administered to patients with advanced colorectal cancer without unacceptable toxicity.;Secondary Objective: - To evaluate treatment efficacy in terms of objective response. - To evaluate treatment efficacy in terms of progression free survival and overall survival. Exploratory objectives: - To explore biomarkers for: -pTTL persistence in vivo. -pTTL anatomical localisation of pTTL post infusion, with focus on tumour infiltration. -pTTL recognition of neoantigens in vivo and pTTL capacity to achieve tumour cell eradication - pTTL characteristics -To gain early insights in selection of neoantigens. Data on the association between the selected neoantigens, biomarker evaluation and clinical outcome will be collected. ;Primary end point(s): The primary endpoint is safety with adverse events (AEs) assessed according to CTCAE v.5. Special focus will be placed on immunological AEs and AEs known to be associated with T cell therapies, which are classified as AEs of special interest (AESI). AESI will include autoimmune reactions potentially resulting from off-target toxicity such as colitis, and immune-mediated reactions associated with immune cell activation, such as cytokine release syndrome (CRS).;Timepoint(s) of evaluation of this end point: Evaluated through: - AE reporting and questioning (done regularly during the study from visit 2 until last follow-up). - Physical examinations (done regularly during the study from screening until week 26 after treatment administration). - Vital signs (done regularly during the study from screening until until week 26 after treatment administration). - Safety laboratory parameters (done regularly during the study from screening until week 26 after treatment administration). - Electrocardiogram (ECG) (done regularly during the study from visit 3 until day 23 after treatment administration). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Objective response (according to iRECIST). • Characterisation of treatment response: o time to response o duration of response • Time to tumour progression assessed using the iRECIST criteria (time from inclusion in Part II of the trial until disease progression). • Kinetics of tumour progression/growth (compared to pre-treatment) • Overall survival (time from inclusion to death of any cause). • Progression-free survival (time from inclusion to tumour progression or death of any cause). • Disease-specific survival (time to death of disease). Exploratory endpoints: • Evaluation of biomarkers for: o pTTL persistence. T cell receptor sequencing (TCRseq) will be used to characterise the pTTL product and to trace the identified pTTL clones in sequential peripheral blood samples post treatment. o pTTL tumour infiltration. If feasible, pre- and post-treatment biopsies will be taken for histological assessment of T cell infiltration and characterisation of tumour-infiltrating T cells. o pTTL neoantigen specificity and efficacy: ? Functional T cell assays will be used to evaluate neoantigen-specific responses in the pTTL product and in peripheral blood T cells. The evaluation plan includes investigation of potential tumour killing assays. ? Markers of tumour burden will be evaluated. o pTTL characteristics: analysis of the pTTL product and of post therapy peripheral blood samples will be performed to evaluate the functional status, differentiation and lineage-identity of T cells and other immune cells. • Correlation of neoantigen selection to clinical outcome. The type of neoantigens targeted will be assessed in the context of clinical outcomes, signals of efficacy and biomarker evaluation. ;Timepoint(s) of evaluation of this end point: Evaluated through medical imaging and iRECIST assessment. Medical imaging done at visit 2 prior to surgery, visit 3 prior to treatment, and at week 6, 12, 18 and 24. Also done at month 9, 12, 18 and | — |
Countries
Sweden
Contacts
Public ContactClinical Research Manager
CTC Clinical Trial Consultants AB
Outcome results
None listed