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

Официальное название

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)

Обзор

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.

Вмешательства

• Биопрепарат STC-1010 + IS regimen + SOC therapy
  STC-1010 administered with immunostimulants (IS) in low-dose (cyclophosphamide and GM-CSF) and standard of care (SOC) therapy (mFOLFOX6 with or without bevacizumab)

Первичные конечные точки

• Phase 1: To determine overall safety profile, recommended Phase 2 dose (RP2D) and maximum tolerated dose (MTD) [Срок оценки: 28 days]
• Phase 2A: To determine the clinical efficacy by Progression Free Survival (PFS) rate [Срок оценки: 12 months]

Вторичные конечные точки (9)

• Phase 1: To determine the preliminary clinical efficacy [Срок оценки: 6 months]
• Phase 1: To describe the effects on cell-mediated immunity [Срок оценки: Up to 72 hours post injection]
• Phase 2A: To determine the overall safety and tolerability profile [Срок оценки: 6, 12 and 24 months]
• Phase 2A: To determine the clinical efficacy by Clinical Benefit Rate (CBR) [Срок оценки: 12 and 24 months]
• Phase 2A: To determine the clinical efficacy by Objective Response Rate (ORR) [Срок оценки: 6, 12 and 24 months]
• Phase 2A: To determine the clinical efficacy by Duration of Response (DOR) [Срок оценки: 6,12 and 24 months]
• Phase 2A: To determine the clinical efficacy by Progression Free Survival (PFS) [Срок оценки: 6,12 and 24 months]
• Phase 2A: To determine the clinical efficacy by Overall Survival (OS) [Срок оценки: 12 and 24 months]
• Phase 2A: To determine the clinical efficacy by metastases resection rate [Срок оценки: Up to 18 months]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 7 центров

• Institut Bergonié — Bordeaux
• Centre Georges François Leclerc (CGFL) — Dijon
• Centre Léon Bérard (CLB) — Lyon
• Hospices Civils de Lyon (HCL) — Lyon
• Institut du Cancer de Montpellier (ICM) — Montpellier
• Centre Hospitalier Universitaire de Poitiers (CHU) — Poitiers
• Institut Gustave Roussy (IGR) — Villejuif

США · 1 центр

• Johns Hopkins — Baltimore

Бельгия · 1 центр

• Institut Jules Bordet — Brussels

Идентификаторы

NCT: NCT06934538 · BreAK CRC-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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