First use of STC-1010 immunotherapy with standard chemotherapy for unresectable locally advanced or metastatic colorectal cancer

Open Label, Multicenter, Dose-escalation and Cohort-expansion Phase I/IIA Trial of STC-1010, an Immunotherapy, in Patients With Unresectable Locally Advanced or Metastatic Colorectal Cancer (CRC) - BreAK CRC Trial (BreAK for Brenus Anti-cancer)

This trial will test whether adding a new immunotherapy called STC-1010 plus immune stimulants to standard chemotherapy helps people with unresectable locally advanced or metastatic colorectal cancer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Brenus Pharma (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, bevacizumab, cyclophosphamide
• Locations: 9 sites (Baltimore, Maryland and 8 other locations)
• Trial ID: NCT06934538 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, open-label Phase I/IIa trial combining STC-1010 with an immunostimulant regimen (GM-CSF and low-dose cyclophosphamide) given alongside standard mFOLFOX6 chemotherapy with or without bevacizumab. Phase I uses dose escalation and a small expansion to define the maximum tolerated dose and recommended Phase II dose, enrolling about 21–33 participants in Europe, followed by a Phase IIa expansion to further evaluate safety and early efficacy. Participants must have unresectable locally advanced (stage IIIC, T4b) or metastatic (stage IV) colorectal adenocarcinoma with measurable disease and an ECOG performance status of 0–1, and will undergo baseline and on-treatment biopsies when feasible. The study is multicenter with response assessed by RECIST 1.1 and close safety monitoring throughout treatment.

Who should consider this trial

Good fit: Adults 18–75 with histologically confirmed unresectable locally advanced (T4b) or metastatic colorectal adenocarcinoma, measurable disease, ECOG 0–1 (and ECOG 0 if over 70), who can undergo biopsies and receive mFOLFOX6 with or without bevacizumab are the intended candidates.

Not a fit: Patients with poor performance status (ECOG >1), very limited life expectancy, resectable disease, inability to undergo required biopsies, or who cannot receive standard mFOLFOX6 are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the regimen could improve tumor response and extend disease control beyond what standard chemotherapy alone achieves.

How similar studies have performed: This is a first-in-human combination; while checkpoint immunotherapy benefits MSI-high colorectal cancer, most immunotherapy approaches have had limited success in unselected metastatic colorectal cancer, so this specific regimen is largely untested.

Eligibility criteria

Inclusion Criteria:

1. Male or female aged 18-75 years
2. Histologically confirmed diagnosis of unresectable locally advanced (stage IIIC, T4b) or unresectable metastatic (stage IV) (R0) adenocarcinoma of the colon or rectum
3. Adjuvant fluoropyrimidine monotherapy or oxaliplatin-based chemotherapy allowed if more than 6 months have elapsed between the end of adjuvant treatment and first relapse
4. Determination of KRAS and BRAF mutation status
5. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
6. 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
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1. Participants \>70 years must have a PS= 0.
8. Life expectancy \> 3 months as assessed by the investigator
9. Effective contraceptive measures implemented

Exclusion Criteria:

1. Patients with symptomatic ascites or pleural effusion
2. Dihydropyrimidine dehydrogenase (DPD) deficiency
3. Resectable tumor with curative intent or patient considered for a curative strategy by intensifying chemotherapy to induce resectability
4. Prior chemotherapy for metastatic disease
5. Prior immunotherapy for advanced/metastatic disease (except for Arm 2A-2)
6. Prior therapy with an investigational agent
7. BRAF mutation
8. Active auto-immune diseases such as rheumatoid arthritis, lupus, Crohn's disease, ulcerative colitis
9. Medical conditions requiring immunosuppressive therapy
10. Major surgery \<4 weeks prior to first administration of STC-1010
11. Radiotherapy \< 4 weeks prior to first administration of STC-1010 or \< 2 weeks in case of palliative radiotherapy
12. Prior stem cell or solid organ transplantation
13. Dementia or altered mental status or subject of a legal protection measure that would prohibit informed consent
14. Active drug or alcohol abuse as assessed by the Investigator
15. 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.

Where this trial is running

Baltimore, Maryland and 8 other locations

• Johns Hopkins — Baltimore, Maryland, United States (Not_yet_recruiting)
• Institut Jules Bordet — Brussels, Belgium (Not_yet_recruiting)
• Institut Bergonié — Bordeaux, France (Recruiting)
• Centre Georges François Leclerc (CGFL) — Dijon, France (Recruiting)
• Centre Léon Bérard (CLB) — Lyon, France (Not_yet_recruiting)
• Hospices Civils de Lyon (HCL) — Lyon, France (Recruiting)
• Institut du Cancer de Montpellier (ICM) — Montpellier, France (Recruiting)
• Centre Hospitalier Universitaire de Poitiers (CHU) — Poitiers, France (Not_yet_recruiting)
• Institut Gustave Roussy (IGR) — Villejuif, France (Recruiting)

Study contacts

• Study coordinator: Corinne TORTORELLI, Pharm.D, Ph.D

Conditions Unresectable Metastatic Colorectal Cancer; Unresectable Locally Advanced Colorectal Cancer