A First-In-Human Trial of the novel T cell Immunotherapy pTTL in Patients with Advanced Colorectal Cancer
- Conditions
- Stage IV colorectal cancer.MedDRA version: 21.0Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-000394-96-SE
- Lead Sponsor
- EOGAP Therapeutics AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 16
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 < 1.5 x ULN (does not apply to patients with Gilberts Syndrome)
d.AST and ALT = 1.5 x ULN (or = 5 x ULN in the presence of liver metastases)
e.Serum creatinine = ULN (if serum creatinine is between 1 and 1.5 x ULN, patients may be eligible provided that the calculated GFR is at least 35 mL/min using Cockcroft-Gault method).
f.Albumin =24 g/L
9 (no 10 in part 2). Patients of childbearing potential or their partners of childbearing potential must be willing to take the appropriate precaution to avoid pregnancy or fathering a child for the duration of Part II and practice an approved, highly effective method of birth control during treatment and for 6 months after receiving pTTL. For patients of childbearing potential, appropriate precautions to avoid pregnancy is required also in Part I, as pregnancy would preclude proceeding to Part II of the trial.
Inclusion criteria in addition to the above
Applicable only for Part I:
10. Able to undergo surgery or biopsy to obtain tumour tissue for neoantigen evaluation and to retrieve RNs as starting material for pTTL manufacturing
11. The area from which the RLN will be obtained shall not have been exposed to radiotherapy.
Applicable only for Part 2:
6. Have received all possible standard of care therapies, OR further standard of care therapies are currently not considered to be in the patient’s best interest, OR toxicity from previous therapy limits the choice of suitable standard of care therapy OR scheduled pause in palliative standard of care therapy as judged by the Investigator.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method