BreAK CRC (001) trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Brenus Pharma

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Neoplasms [C04]

Trial duration

17 Jun 2025 → ongoing

Decision date (initial)

2025-10-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

Primary objectives for the Phase I: To characterize the overall safety profile of the STC-1010 + IS regimen administered with SOC therapy to participants with unresectable locally advanced or metastatic CRC and to determine the RP2D and the MTD.
Primary objectives for the Phase IIA: To determine the clinical efficacy of STC-1010 + IS regimen when administered with SOC therapy to participants with locally advanced or metastatic unresectable CRC.

Conditions and MedDRA coding

Unresectable locally advanced or metastatic colorectal cancer

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Federal Agency For Medicines And Health Products, Agence Nationale de Sécurité du Médicament et des poduits de santé, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Male or female aged 18-75 years
2. Life expectancy > 3 months as assessed by the investigator
3. Clinical labs a. Hematology: • Lymphocyte count > 1 000/mm3 • Absolute neutrophil count ≥ 1 500 /μL • Hemoglobin > 9 g/dL • Platelet count ≥ 100 000/μL b. Liver enzymes: • aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 × upper limit of normal (ULN) (or ≤ 5 × ULN in participants with liver metastases) • bilirubin ≤ 1.5 × ULN (or ≤ 3 ULN in participants with Gilbert’s disease) c. Renal function: • serum creatinine ≤ 1.5 × ULN • Estimated glomerular filtration rate (GFR) > 50 mL/min/1,73m2
4. Coagulation parameters: APTT<1.5 N or Prothrombin rate > 70%
5. Contraceptives measures a. Women of childbearing potential (WOCBP) must: • have a negative pregnancy test collected during screening period and within 1 week before first dose of study drug • use 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 • agree 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 • agree 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: • agree 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 • agree to not donate sperm during the study and for at least 12 months after the last study drug administration • no plan to father a child during the study and within 12 months after the last study drug administration
6. Participants affiliated to social security insurance (if applicable, in accordance to local regulations)
7. 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).
8. Specific Inclusion Criteria Phase I and Phase IIA for Arm 2A-1: Participants eligible for 1st line treatment with mFOLFOX6 + bevacizumab
9. 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
10. 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).
11. Voluntarily signed written informed consent before performance of any study-specific screening procedures
12. Histologically confirmed diagnosis of unresectable locally advanced (stage IIIC, T4b) or unresectable metastatic (stage IV) adenocarcinoma of the colon or rectum
13. Participants MHC/HLA of Class I positive (inclusion of patients with intermediate or high score, semiquantitative test only on tumor biopsy)
14. Adjuvant fluoropyrimidine monotherapy or oxaliplatin-based chemotherapy allowed if more than 6 months have elapsed between the end of adjuvant treatment and first relapse
15. Determination of KRAS and BRAF mutation status
16. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
17. 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
18. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1. Participants >70 years must have a PS= 0.

Exclusion criteria 27

1. Patients with symptomatic ascites or pleural effusion
2. 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
3. Active auto-immune diseases such as rheumatoid arthritis, lupus, Crohn’s disease, ulcerative colitis
4. Medical conditions requiring immunosuppressive therapy
5. Major surgery <4 weeks prior to first administration of STC-1010
6. Radiotherapy < 4 weeks prior to first administration of STC-1010 or < 2 weeks in case of palliative radiotherapy
7. Prior stem cell or solid organ transplantation
8. Live vaccination within 4 weeks prior to first administration of STC-1010
9. Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment 4 weeks before STC-1010 administration
10. Known/suspected hypersensitivity to monoclonal antibodies, therapeutic proteins, or immunotherapy
11. 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
12. Dihydropyrimidine dehydrogenase (DPD) deficiency
13. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study assessed by the investigator
14. 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 .
15. Active or chronic infection by human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
16. 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
17. Dementia or altered mental status or subject of a legal protection measure that would prohibit informed consent
18. Active drug or alcohol abuse as assessed by the Investigator
19. 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.
20. Resectable tumor with curative intent or patient considered for a curative strategy by intensifying chemotherapy to induce resectability
21. Prior chemotherapy for metastatic disease
22. Prior immunotherapy for advanced/metastatic disease (except for Arm 2A-2)
23. Prior therapy with an investigational agent
24. BRAF mutation
25. 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. supportive care corticosteroids given occasionally with SoC are accepted (e.g., SoS corticosteroids on day 1 combined with setrons and tryptans).
26. Ongoing administration of acetylsalicylic acid at dose ≥ 325 mg/day
27. Symptomatic Peritoneal Carcinomatosis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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).
2. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Brenus Pharma

Sponsor organisation

Brenus Pharma

Address

4 Rue Eric De Cromieres

City

Clermont Ferra

Postcode

63000

Country

France

Scientific contact point

Organisation

Brenus Pharma

Contact name

Benoit PINTEUR

Public contact point

Organisation

Brenus Pharma

Contact name

Benoit PINTEUR

Locations

2 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications