colorectal cancer at a metastatic stage, eligible for a second line treatment and presenting with a constitutive BRAF or RAS mutation MedDRA version: 21.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: IN01
Pharmaceutical Form: Emulsion and suspension for emulsion for injection
INN or Proposed INN: IN01
Other descriptive name: IN01
Concentration unit: mg/ml milligram(s)/millilitre
Conc
Sponsors
IN3BIO
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: Characterize the safety, tolerability and immunogenicity of IN01 in combination with a small molecule inhibitor to confirm the recommended Phase II treatment dose and schedule Phase II: Further assess the efficacy in the different selected mCRC genotypes based on tumour response, biomarkers and survival. Some biomarker collection and/or analysis may be limited to selected sites and patients;Secondary Objective: Phase I: Assess the pharmacodynamic and efficacy (proof-of-concept) on biomarkers, tumour response and survival in different selected mCRC genotypes. Some biomarker collection and/or analysis may be limited to selected sites and patients Phase II: • Confirm the safety profile • Confirm the immunogenicity profile • Assess the patient reported outcomes (PROs) including solicited adverse reactions and quality of life;Primary end point(s): Phase I: • Proportion of patients achieving an anti-EGF antibody immune response • Dose limiting toxicity rates Phase II: Objective response rate (ORR: complete and partial responses) according to RECIST 1.1;Timepoint(s) of evaluation of this end point: Phase I: every 2 weeks for 6 weeks after treatment start Phase II: every 8 weeks from treatment start untill end of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I: • Treatment emergent Adverse-event (TEAE) per System Organ Class (SOC) and Preferred Terms (PT) and laboratory toxicity rates per CTCAE grade • Anti-EGF antibody kinetic profile • Absolute and relative changes in circulating EGF level over time Phase II: • Median duration of response according to RECIST 1.1 • Treatment emergent Adverse-event (TEAE) and per SOC and PT and laboratory toxicity rates per CTCAE grade • Absolute and relative changes in circulating EGF level over time • Anti-EGF antibody kinetic profile • Tumour shrinkage rate (at least 15% shrinkage of tumour diameter defined as relation of the smallest sum of tumour diameter to baseline) • median depth of response (maximum relative shrinkage of target lesions defined as relation of the smallest sum of tumour diameter to baseline) • Median progression free survival (PFS: time to PD or death due to any cause) • Progression-free survival rates at 3, 6 and 12 months • Median overall survival (OS: time to death due to any cause) • Overall survival rates at 3, 6, 12 and 18 months;Timepoint(s) of evaluation of this end point: Phase I and Phase II: Every 2 weeks for the first 8 weeks and every 8 weeks after | — |
Countries
Bulgaria
Contacts
Public ContactHead of Clinical Development
IN3BIO
Outcome results
None listed