Study of Denikitug (GS-1811) Given Alone or With Nivolumab or With Chemotherapy in Adults With Advanced Colorectal Cancer

Официальное название

A Phase 2, Open Label, Multicenter, Randomized Study, to Evaluate the Efficacy and Safety of Denikitug Monotherapy and Denikitug-based Combinations in Participants With Advanced Microsatellite Stable (MSS) Colorectal Cancer (CRC)

Обзор

The goal of this clinical study is to learn more about the study drug, Denikitug (DEN, GS-1811), to evaluate the efficacy and safety of Denikitug Monotherapy and Denikitug-based Combinations in participants with advanced microsatellite stable (MSS) colorectal cancer (CRC). The primary objective of this study is to assess the effect of DEN as monotherapy and in combination with nivolumab (NIVO) or trifluridine-tipiracil (FTD-TPI) and bevacizumab (BVZ) on objective response rate (ORR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1).

Вмешательства

• Препарат Denikitug
  Administered Intravenously
• Препарат Nivolumab
  Administered Intravenously
• Препарат Bevacizumab
  Administered Intravenously
• Препарат Trifluridine-Tipiracil
  Administered orally

Первичные конечные точки

• Objective Response Rate (ORR) [Срок оценки: Up to 60 months]

Вторичные конечные точки (9)

• Duration of response (DOR) [Срок оценки: Up to 60 months]
• Progression-Free Survival (PFS) [Срок оценки: Up to 60 months]
• Overall Survival (OS) [Срок оценки: Up to 60 months]
• Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [Срок оценки: First dose date up to 120 days post last dose, up to 60 months]
• Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0 [Срок оценки: First dose date up to 120 days post last dose, up to 60 months]
• Pharmacokinetic (PK) Parameter: Serum concentration of Denikitug [Срок оценки: Up to 36 months]
• PK Parameter: Cmax for Denikitug [Срок оценки: Up to 36 months]
• PK Parameter: AUCall for Denikitug [Срок оценки: Up to 36 months]
• Percentage of Participants who Developed Antidrug Antibody (ADA) Against Denikitug [Срок оценки: Up to 36 months]

Критерии участия

Критерии включения

Medical History/Physical Characteristics

• Histologically or cytologically confirmed unresectable, recurrent, or locally advanced or metastatic microsatellite stable colorectal cancer (MSS CRC) (adenocarcinoma, excluding appendix cancer).
• Documented MSS or proficient mismatch repair (pMMR) disease by local assessment using a validated polymerase chain reaction (PCR) (microsatellite status) and/or immunohistochemistry (IHC) mismatch repair (MMR) assay is required.
• Has received up to 2 prior lines of systemic therapy for advanced or metastatic CRC, which must have included at least fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapies if indicated; and if applicable: anti-vascular endothelial growth factor (VEGF) therapy, anti epidermal growth factor receptor (EGFR) therapy, encorafenib or adagrasib/sotorasib.
• Documented progressive disease (PD) by computed tomography (CT) or magnetic resonance imaging (MRI) during or after the most recent therapy per RECIST Version 1.1 criteria by investigator assessment.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.

Laboratory Assessments

• Have adequate organ function.

Key Exclusion Criteria with:

Medical Conditions/History:

• Significant cardiovascular disease.
• History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years.
• History of (noninfectious) pneumonitis/interstitial lung disease or current pneumonitis/ interstitial lung disease.
• History of gastrointestinal (GI) perforation, permanent ileostomy, abdominal abscess or fistula within 6 months, active or uncontrolled GI bleeding within 4 weeks, or any condition associated with significant risk of bleeding or perforation (eg, untreated varices, tumor erosion, recent GI surgery).

Prior/Concurrent Therapy or Clinical Study Experience

Prior treatment with:

• Trifluridine-tipiracil, regorafenib, or fruquitinib.
• Any immuno-oncology therapy.
• Anticancer biologic agent within 4 weeks prior to randomization or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to randomization and have not recovered (ie, Grade 2 or less) from AEs from prior anticancer therapy at the time of randomization. Individuals in observational studies are eligible.
• Allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 6 центров

• Yale-New Haven Hospital - Yale Cancer Center — North Haven
• Beth Israel Deaconess Medical Center — Boston
• Dana-Farber Cancer Institute — Boston
• Washington University School of Medicine — St Louis
• Avera Cancer Institute — Sioux Falls
• University of Virginia, — Charlottesville

South Korea · 4 центра

• Samsung Medical Center — Busan
• Seoul National University Hospital — Seoul
• Yonsei University Severance Hospital ( aka Yonsei Cancer Center) — Seoul
• Asan Medical Center — Seoul

Австралия · 3 центра

• Chris O'Brien Lifehouse — Camperdown
• Royal Brisbane and Women's Hospital — Herston
• Peter MacCallum Cancer Centre — Melbourne

Испания · 1 центр

• Hospital General Universitario Gregorio Maranon — Madrid

Идентификаторы

NCT: NCT07527858 · GS-US-741-7756 · 2025-523984-39

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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