HCT116-A, HCT116-B, HT-29-A, HT-29-B, LOVO-B, LOVO-A for Colorectal cancer (unresectable locally advanced or metastatic)

Inclusion criteria

• {"criterion_text":"- Male or female aged 18-75 years\n- Voluntarily signed written informed consent before performance of any study-specific screening procedures\n- Histologically confirmed diagnosis of unresectable locally advanced (stage IIIC, T4b) or unresectable metastatic (stage IV) (R0) adenocarcinoma of the colon or rectum\n- Participants MHC/HLA of Class I positive (inclusion of patients with intermediate or high score, semiquantitative test only on tumor biopsy)\n- Adjuvant fluoropyrimidine monotherapy or oxaliplatin-based chemotherapy allowed if more than 6 months have elapsed between the end of adjuvant treatment and first relapse\n- Determination of KRAS and BRAF mutation status\n- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)\n- Must agree to have biopsy at screening and on-treatment, only if not representing an unacceptable clinical risk and/or if technically feasible as judged by the Investigator in discussion with the interventional radiologist or endoscopist\n- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1. Participants >70 years must have a PS= 0.\n- Life expectancy > 3 months as assessed by the investigator\n- Clinical labs a. Hematology: •\tLymphocyte count > 1 000/mm3 •\tAbsolute neutrophil count ≥ 1 500 /μL •\tHemoglobin > 9 g/dL •\tPlatelet count ≥ 100 000/μL b. Liver enzymes: •\taspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 × upper limit of normal (ULN) (or ≤ 5 × ULN in participants with liver metastases) •\tbilirubin ≤ 1.5 × ULN (or ≤ 3 ULN in participants with Gilbert’s disease) c. Renal function: •\tserum creatinine ≤ 1.5 × ULN •\tEstimated glomerular filtration rate (GFR) > 50 mL/min/1,73m2\n- Coagulation parameters: ACT<1.5 N or Prothrombin rate > 70%\n- Contraceptives measures a. Women of childbearing potential (WOCBP) must: •\thave a negative pregnancy test within 1 week before first dose of study drug •\tuse highly effective method(s) of birth control consistently and correctly during the study and for at least 12 months after the last dose of study drug •\tagree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 12 months after the last study drug administration •\tagree to not breastfeed and not plan to become pregnant during the study and for at least 12 months after the last study drug administration b. Males who are sexually active must: •\tagree to use a condom with spermicidal foam/gel/film/cream/suppository during the study and for at least 12 months after the last dose of study drug •\tagree to not donate sperm during the study and for at least 12 months after the last study drug administration •\tno plan to father a child during the study and within 12 months after the last study drug administration\n- Participants affiliated to social security insurance (if applicable, in accordance to local regulations)\n- Specific Inclusion Criteria Phase I and phase IIA for Arm 2A-1: Participants with documented MSS/pMMR tumors, based on the immunohistochemistry (IHC) or molecular biology upon diagnosis (as managed for participants receiving 5FU).\n- Specific Inclusion Criteria Phase I and Phase IIA for Arm 2A-1: Participants eligible for 1st line treatment with mFOLFOX6 + bevacizumab\n- Specific Inclusion Criteria Phase IIA for Arm 2A-2: Participants with unresectable locally advanced (Stage IIIC, T4b) or metastatic (stage IV) unresectable (R0) CRC, including Lynch syndrome, who have progressed to 1 prior line of immunotherapy administered for a minimum of 4 months\n- Specific Inclusion Criteria Phase IIA for Arm 2A-2 MSI-H/dMMR documented by IHC or molecular biology at diagnosis (as managed for participants receiving 5FU)."}

Exclusion criteria

• {"criterion_text":"- Patients with symptomatic ascites or pleural effusion\n- Participants with rapidly progressing disease defined as advanced/metastatic, symptomatic, visceral spread, with a risk of life-threatening complications in the short term (e.g., during screening period) that includes participants with massive uncontrolled pleural, pericardial, peritoneal effusion, pulmonary lymphangitis, and over 50% liver involvement\n- Active auto-immune diseases such as rheumatoid arthritis, lupus, Crohn’s disease, ulcerative colitis\n- Medical conditions requiring immunosuppressive therapy\n- Major surgery <4 weeks prior to first administration of STC-1010\n- Radiotherapy < 4 weeks prior to first administration of STC-1010 or < 2 weeks in case of palliative radiotherapy\n- Prior stem cell or solid organ transplantation\n- Live vaccination within 4 weeks prior to first administration of STC-1010\n- Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment within 4 weeks of STC-1010 administration\n- Known/suspected hypersensitivity to monoclonal antibodies, therapeutic proteins, or immunotherapy\n- Clinically significant cardiac disease including heart failure (New York Heart Association, Class III or IV), pre-existing arrhythmia, unstable angina pectoris, or myocardial infarction within 1 year before study entry, or clinically significant ECG abnormalities\n- Dihydropyrimidine dehydrogenase (DPD) deficiency\n- Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study assessed by the investigator\n- Patient with uncontrolled and symptomatic brain metastases. Participants with asymptomatic brain metastases are allowed provided they are stable and off therapeutic steroids for at least 2 weeks .\n- Active or chronic infection by human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)\n- Second malignancy (except adequately treated non-melanoma skin cancer, in situ tumors of cervix/breast , bladder cancer, etc.) unless it has undergone potentially curative therapy with no evidence of recurrence for > 2 years prior to administration of STC-1010\n- Dementia or altered mental status or subject of a legal protection measure that would prohibit informed consent\n- Active drug or alcohol abuse as assessed by the Investigator\n- Participant deprived of their liberty by a judicial or administrative decision, undergoing psychiatric care and admitted to a health or social establishment for purposes other than research.\n- Resectable tumor with curative intent or patient considered for a curative strategy by intensifying chemotherapy to induce resectability\n- Prior chemotherapy for metastatic disease\n- Prior immunotherapy for advanced/metastatic disease (except for Arm 2A-2)\n- Prior therapy with an investigational agent\n- BRAF mutation\n- Concomitant systemic corticosteroid at a daily dose of > 10 mg of prednisone or equivalent. Low-dose corticosteroids allowed if patient has been on a stable dose with stable symptoms for at least 4 weeks prior to first STC-1010 administration\n- Ongoing administration of acetylsalicylic acid at dose ≥ 325 mg/day"}

Primary endpoints

• {"endpoint_text":"- Primary end point for the Phase I: Incidence, severity, and relationship of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Dose-Limiting Toxicities (DLT) (in dose escalation part), AEs leading to treatment discontinuation; and clinically significant findings on clinical laboratory tests, vital signs, ECGs, and physical examinations, using the Common Terminology Criteria for Adverse Events (CTCAE Version 5).","definition_or_measurement_approach":"Safety events (TEAEs, SAEs, DLTs, AEs leading to discontinuation) and clinically significant findings will be assessed and graded using CTCAE v5; clinical labs, vital signs, ECGs and physical examinations will be used to characterize safety."}
• {"endpoint_text":"- Primary endpoint for the Phase IIa: PFS rate at 12 months from STC-1010 IS treatment initiation, defined as the proportion of participants alive and without progression (i.e., participants with CR, PR or SD) at 12 months according to RECIST 1.1","definition_or_measurement_approach":"Progression-free survival (PFS) rate at 12 months measured as proportion of participants alive and without progression (CR, PR or SD) at 12 months per RECIST 1.1."}

France

Earliest CTIS Part Ii Submission Date

12-08-2024

Latest Decision Or Authorization Date

16-04-2025

Processing Time Days

247

Number Of Sites

7

Number Of Participants

69

Belgium

Earliest CTIS Part Ii Submission Date

23-09-2025

Latest Decision Or Authorization Date

06-10-2025

Processing Time Days

13

Number Of Sites

1

Number Of Participants

10

Primary sponsor

Full Name

Brenus Pharma

Organisation Type

Pharmaceutical company

Country Of Registered Address

France