First-in-human Trial of STC-1010, an Immunotherapy, in Patients With Unresectable Locally Advanced or Metastatic Colorectal Cancer

Phase 2RecruitingNCT06934538

Brenus Pharma90 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Unresectable Metastatic Colorectal Cancer Unresectable Locally Advanced Colorectal Cancer

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (9)

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

Outcomes

Primary Outcomes

Phase 1: To determine overall safety profile, recommended Phase 2 dose (RP2D) and maximum tolerated dose (MTD)

Endpoint/Outcome Measures: 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, electrocardiograms (ECGs), and physical examinations, using the Common Terminology Criteria for Adverse Events (CTCAE Version 5).

Time frame: 28 days

Phase 2A: To determine the clinical efficacy by Progression Free Survival (PFS) rate

Progression Free Survival (PFS) rate at 12 months from STC-1010 + IS regimen initiation, defined as the proportion of participants alive and without progression (i.e., participants with complete response \[CR\], partial response \[PR\] or stable disease \[SD\]) at 12 months according to RECIST 1.1

Time frame: 12 months

Secondary Outcomes

Phase 1: To determine the preliminary clinical efficacy

Endpoints/Outcome Measures: Overall Response Rate (ORR) at 6 months from STC-1010 + IS treatment initiation, defined as the achievement of either a complete response (CR) or partial response (PR) according to RECIST 1.1; Progression Free Survival (PFS) rate at 6 months from STC-1010 + IS treatment initiation (defined as the rate of participants alive with CR, PR or SD) according to RECIST 1.1; and Median of PFS.

Time frame: 6 months

Phase 1: To describe the effects on cell-mediated immunity

Assessment of delayed-type hypersensitivity (DTH) score after the first vaccination (at 1, 24, 48 and 72 hours post-STC-1010 injection) and then after the 4th, 8th and every boost

Time frame: Up to 72 hours post injection

Phase 2A: To determine the overall safety and tolerability profile

Endpoints/Outcome Measures: Incidence, severity and relationship of TEAEs, SAEs, TEAEs leading to discontinuation of study treatment; and clinically significant findings on clinical laboratory tests, vital signs, ECGs and physical examinations, using the CTCAE Version 5.

Time frame: 6, 12 and 24 months

Phase 2A: To determine the clinical efficacy by Clinical Benefit Rate (CBR)

Clinical Benefit Rate (CBR) defined as the percentage of participants in whom the best response is CR or PR, or SD lasting for a least 6 months.

Time frame: 12 and 24 months

Phase 2A: To determine the clinical efficacy by Objective Response Rate (ORR)

Objective Response Rate (ORR) defined as the proportion of patients who achieve a complete or partial response per RECIST 1.1 criteria. Patients with unevaluable or unknown response status will be considered as non-responders.

Time frame: 6, 12 and 24 months

Phase 2A: To determine the clinical efficacy by Duration of Response (DOR)

Duration of response (DOR), defined as the time from first documented evidence of CR or PR to the earliest date of documented radiological progression or death due to any cause

Time frame: 6,12 and 24 months

Phase 2A: To determine the clinical efficacy by Progression Free Survival (PFS)

Progression Free Survival (PFS) defined as the time to the date of progression or death from any cause. The median PFS with it's 95% confidence interval (CI) will also be calculated

Time frame: 6,12 and 24 months

Phase 2A: To determine the clinical efficacy by Overall Survival (OS)

Overall Survival (OS) defined as the time to the date of death from any cause. The median OS with its 95% CI will also be calculated.

Time frame: 12 and 24 months

Phase 2A: To determine the clinical efficacy by metastases resection rate

Metastases resection rate defined as the percentage of participants who undergo resection

Time frame: Up to 18 months

First-in-human Trial of STC-1010, an Immunotherapy, in Patients With Unresectable Locally Advanced or Metastatic Colorectal Cancer

Overview

Conditions

Interventions

Eligibility

Locations (9)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts