Clinical trial NCT06934538: First-in-human Trial of STC-1010, an Immunotherapy, in Patients With Unresectable Locally Advanced or Metastatic Colorectal Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Unresectable Metastatic Colorectal Cancer
Unresectable Locally Advanced Colorectal Cancer
Lead sponsor: Brenus Pharma
Sponsor class: INDUSTRY
First posted: 2025-04-18
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a phase I/IIA, first-in-human (FIH), two-part, open-label, multicenter study to characterize the safety, tolerability profile, and clinical efficacy of STC-1010 associated with GM-CSF and cyclophosphamide immunostimulant (IS) regimen administered with standard of care (SOC) therapy (mFOLFOX6 with or without bevacizumab) to participants with unresectable locally advanced (stage IIIC, T4b) or unresectable metastatic (stage IV) colorectal cancer (CRC).

The trial will be conducted in two parts:

* A Phase I consisting of a dose escalation part and small expansion part to determine the maximum tolerated dose (MTD), recommended Phase II dose (RP2D) and safety profile of the STC-1010 + IS regimen administered with SOC therapy. Approximately 21 to 33 participants will be included in this phase in Europe.
* A Phase IIA consisting of the expansion stage of the study which will further evaluate the clinical efficacy and safety of STC-1010 on a larger number of participants treated at the identified RP2D. Approximately 57 to 60 participants will be enrolled in total in 2 different arms. Multi-site recruitment will take place in Europe and in the US.


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.

Primary outcomes:
measure: Phase 1: To determine overall safety profile, recommended Phase 2 dose (RP2D) and maximum tolerated dose (MTD)
timeFrame: 28 days
measure: Phase 2A: To determine the clinical efficacy by Progression Free Survival (PFS) rate
timeFrame: 12 months
Secondary outcomes:
measure: Phase 1: To determine the preliminary clinical efficacy
timeFrame: 6 months
measure: Phase 1: To describe the effects on cell-mediated immunity
timeFrame: Up to 72 hours post injection
measure: Phase 2A: To determine the overall safety and tolerability profile
timeFrame: 6, 12 and 24 months
measure: Phase 2A: To determine the clinical efficacy by Clinical Benefit Rate (CBR)
timeFrame: 12 and 24 months
measure: Phase 2A: To determine the clinical efficacy by Objective Response Rate (ORR)
timeFrame: 6, 12 and 24 months
measure: Phase 2A: To determine the clinical efficacy by Duration of Response (DOR)
timeFrame: 6,12 and 24 months
measure: Phase 2A: To determine the clinical efficacy by Progression Free Survival (PFS)
timeFrame: 6,12 and 24 months
measure: Phase 2A: To determine the clinical efficacy by Overall Survival (OS)
timeFrame: 12 and 24 months
measure: Phase 2A: To determine the clinical efficacy by metastases resection rate
timeFrame: Up to 18 months
Other outcomes:
measure: Phase 1: To determine the impact on immune and molecular biomarkers (exploratory outcomes)
timeFrame: At baseline/screening (T0), 1 month, 2 months, 6 months, 12 months
measure: Phase 2: To determine the impact on immune and molecular biomarkers (exploratory outcomes)
timeFrame: At baseline/screening (T0), 1 month, 2 months, 6 months, 12 months and at time of progression (Tprogression, up to 24 months)
Locations:
city: Bordeaux
country: France
facility: Pr Antoine ITALIANO
city: Dijon
country: France
facility: Pr François GHIRINGHELLI
city: Lyon
country: France
facility: Dr Philippe CASSIER
city: Lyon
country: France
facility: Pr Benoit YOU
city: Montpellier
country: France
facility: Dr Diego TOSI
city: Poitiers
country: France
facility: Pr David TOUGERON
city: Villejuif
country: France
facility: Dr Antoine HOLLEBECQUE
Study officials:
References: