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)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 170
- 试验地点
- 14
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •Laboratory Assessments
- •Have adequate organ function.
排除标准
- •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.
研究组 & 干预措施
DEN in combination with Trifluridine-Tipiracil (FTD-TPI) and BVZ (Arm C)
Participants will receive DEN as an IV infusion in combination with BVZ as an IV infusion and FTD-TPI administered orally.
Includes a Safety Run-in cohort (non-randomized cohort) prior to randomization.
干预措施: Trifluridine-Tipiracil (Drug)
Standard of care (SOC) alone: BVZ and FTD-TPI (Arm D)
Participants will receive BVZ as an IV infusion and FTD-TPI administered orally as SOC.
干预措施: Trifluridine-Tipiracil (Drug)
DEN in combination with NIVO (Arm B)
Participants will receive DEN as an IV infusion in combination with NIVO as an IV infusion.
干预措施: Denikitug (Drug)
DEN monotherapy (Arm A)
Participants will receive DEN via intravenous (IV) infusion.
干预措施: Denikitug (Drug)
DEN in combination with Trifluridine-Tipiracil (FTD-TPI) and BVZ (Arm C)
Participants will receive DEN as an IV infusion in combination with BVZ as an IV infusion and FTD-TPI administered orally.
Includes a Safety Run-in cohort (non-randomized cohort) prior to randomization.
干预措施: Bevacizumab (Drug)
Standard of care (SOC) alone: BVZ and FTD-TPI (Arm D)
Participants will receive BVZ as an IV infusion and FTD-TPI administered orally as SOC.
干预措施: Bevacizumab (Drug)
DEN in combination with NIVO (Arm B)
Participants will receive DEN as an IV infusion in combination with NIVO as an IV infusion.
干预措施: Nivolumab (Drug)
DEN in combination with Trifluridine-Tipiracil (FTD-TPI) and BVZ (Arm C)
Participants will receive DEN as an IV infusion in combination with BVZ as an IV infusion and FTD-TPI administered orally.
Includes a Safety Run-in cohort (non-randomized cohort) prior to randomization.
干预措施: Denikitug (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to 60 months
ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST Version 1.1.
次要结局
- Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0(First dose date up to 120 days post last dose, up to 60 months)
- Duration of response (DOR)(Up to 60 months)
- Progression-Free Survival (PFS)(Up to 60 months)
- Overall Survival (OS)(Up to 60 months)
- Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0(First dose date up to 120 days post last dose, up to 60 months)
- Pharmacokinetic (PK) Parameter: Serum concentration of Denikitug(Up to 36 months)
- PK Parameter: Cmax for Denikitug(Up to 36 months)
- PK Parameter: AUCall for Denikitug(Up to 36 months)
- Percentage of Participants who Developed Antidrug Antibody (ADA) Against Denikitug(Up to 36 months)