First in human study assessing the safety, immunogenicity and efficacy of the cancer vaccine IN01 as second line of treatment in RAS and BRAF mutated metastatic colorectal cancer patients

Phase 1

Active, not recruiting

• Conditions: colorectal cancer at a metastatic stage, eligible for a second line treatment and presenting with a constitutive BRAF or RAS mutation; MedDRA version: 21.0Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-004819-31-BG
• Lead Sponsor: IN3BIO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-03-19
• Last Update Posted: 7 June 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Male and female patients, 18 years of age or older
2. With unresectable metastatic (stage IV) histologically or cytologically confirmed adenocarcinoma of the colon or the rectum
3. With at least one constitutive mutation in K or N RAS exon 2 codon 12 or 13, exon 3 codon 59 or 61, or exon 4 codon 117 or 146, or with a constitutive BRAFv600E. mutation (The mutation must have been identified on a tissue biopsy obtained before the first-line treatment or at the first-line treatment starts.)
4. Whose disease progresses after first line cancer treatment regimen
5. Able to take oral medication
6. With eastern cooperative oncology group (ECOG) performance status of = 1 and at least 3 months of expected survival
7. With a baseline lymphocyte count = 1 G/L (1,000/mm3)
8. Who agree to take appropriate precautions to avoid pregnancy/fathering a child from screening to 4 weeks after end of study treatment (males and females alike; except for postmenopausal women for at least 1 year [i.e., spontaneous amenorrhea at least 1 year prior to first IMP administration and confirmed follicle stimulating hormone [FSH] level >40 IU/L], or surgically sterile patients for at least 6 weeks; See 4.2 for more details).
9. Who consented to participate by signing and dating the written informed consent form prior to any study-specific procedures
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 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 56

Exclusion Criteria

1. No baseline measurable lesion (as defined by RECIST 1.1 criteria)
2. Constitutive MSI-high patients (status determined on a tissue biopsy obtained before the first-line treatment or at the first-line treatment start)
3. Still under first line oncological treatment regimen
4. Any contraindication to intra-muscular injection as estimated by the investigator including but not limited to concomitant treatment with an anticoagulant which cannot be temporarily discontinued for allowing safe IN01 injections, as per recommended specific anticoagulant management.
5. Any contraindication (absolute or relative) to the monotherapy treatment with the planned concomitant small inhibitor molecule (trametinib for cohort A or encorafenib for cohort B) according to its approved summary of product characteristics
6. History of other cancer, unless in complete remission and off all chemotherapy and/or radiotherapy for that disease for a minimum of 5 years
7. Use of immunosuppressant drugs such as azathioprine, tacrolimus, cyclosporine, etc. Immunosuppressants are not permitted within 1 month before first IMP administration
8. Administration of any other vaccines with the exception of the influenza and COVID-19 vaccines, within 28 days before first IMP administration
9. Known history of any autoimmune disease
10. Any known primary or secondary immunodeficiencies (e.g. documented Human Immunodeficiency Virus [HIV]) not resolved at least 2 months before IMP administration
11. Treatment with oral, intramuscular or intravenous corticosteroids. Use is not permitted within 7 days before first IMP administration. Inhaled corticosteroids to treat respiratory insufficiency (e.g. chronic obstructive pulmonary disease [COPD]), or topical steroids are permitted
12. History of splenectomy
13. Known incompatibility to both CT scan and MRI
14. Female patients who are pregnant or lactating
15. Any evidence that the patient is unlikely to comply with study treatment, procedures, restrictions or requirements, including uncontrolled systemic or psychiatric diseases (e.g. active infection, uncontrolled hypertension, unstable heart, liver, kidney or metabolic disease) which may compromise the patient’s safety or ability to participate in the study
16. Patients who have received any investigational treatment agent within 28 days before first IMP administration
17. Known allergies, hypersensitivity, or intolerance to the IMP, its excipients or any other vaccine

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified