2025-523984-39-00招募中2 期
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).
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 94
- 试验地点
- 21
- 主要终点
- 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.
研究概览
简要总结
To assess the effect of denikitug (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).
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Medical History/Physical Characteristics MH
- •Histologically or cytologically confirmed unresectable, recurrent, or locally advanced or metastatic 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 the following therapies if indicated and approved/available in the country where the participant is enrolled/randomized. Fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapies; if applicable in combination with: - An anti-VEGF agent (if eligible) or - An anti-EGFR agent (for participants with left sided, B-Raf proto-oncogene (BRAF)/rat sarcoma [RAS] wild-type tumors). Encorafenib in combination with an anti-EGFR agent or encorafenib in combination with an anti-EGFR agent and modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) (if BRAF V600E mutated). Adagrasib or sotorasib in combination with an anti-EGFR agent (if Kirsten rat sarcoma [KRAS] G12C mutated). Note: Perioperative, neoadjuvant, or adjuvant chemotherapy regimens will not count as a prior regimen unless PD has occurred during or within 6 months of completing neoadjuvant/adjuvant therapy. Note: Patients with known human epidermal growth receptor 2 (HER2)-positive tumors are not eligible.
- •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-
- •Have adequate organ function as indicated by the following screening laboratory values: Organ/ Tissue Function: Adequate Hematologic function - Status: Without requiring a transfusion or growth factor within 2 weeks before screening laboratory assessments - Parameters*: ANC: ≥ 1.5 x 109/L ; Platelets: ≥ 100 x 109/L; Hemoglobin: ≥ 9g/dL Adequate hepatic function - Parameters*: Total bilirubin: ≤ 1.5 x ULN or ≤ 3 x ULN in participants with liver metastases or Gilbert’s syndrome or a genetic equivalent; AST and ALT: ≤ 2.5 x ULN or ≤ 5 x ULN if known liver metastases Adequate renal function - Parameters*: Creatinine clearance: ≥ 50 mL/min by the Cockcroft Gault method; The participant`s urinary protein is ≤ 1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥ 2+, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation the study Adequate coagulation - Status: For participants receiving anticoagulant therapy (except platelet anti aggregates) the adequate therapeutic levels of INR should be confirmed - Parameters*:y. INR or PT: ≤ 1.5 x ULN, unless the participant is receiving anticoagulant therapy; aPTT: ≤ 1.5 x ULN, unless the participant is receiving anticoagulant therapy
- •Note: All screening laboratory tests must be reviewed by the investigator and be acceptable prior to enrollment. ALT = alanine aminotransferase; ANC = absolute neutrophil count; aPTT = activated partial thromboplastin time; AST = aspartate aminotransferase; INR = international ratio; PT = prothrombin time; ULN = upper limit of normal
排除标准
- •Medical Conditions/History MC
- •Meet any of the following criteria for cardiovascular disease: Symptomatic cardiac or cerebrovascular disease; cerebral vascular accident/stroke/myocardial infarction or unstable angina pectoris or any other deep arterial thromboembolic events within 6 months of randomization. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication). New York Heart Association (NYHA) Class II or greater congestive heart failure or known left ventricular ejection fraction less than 40%.
- •History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study treatment (eg, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs), any history of noninfectious enteritis or colitis requiring treatment with corticosteroids, or any history of inflammatory bowel disease (including Crohn’s disease or ulcerative colitis) or Celiac disease. Note: Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment as listed above.
- •History of (noninfectious) pneumonitis/interstitial lung disease or current pneumonitis/ interstitial lung disease, including: Radiation pneumonitis requiring steroids. Active or recurrent pneumonitis/interstitial lung disease of any etiology.
- •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 (including anti– programmed cell death ligand 1 [PD (L)1], anti- cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], regulatory T cell (Treg) cell modifying agents, anti-programmed cell death ligand 2, anti- clusters of differentiation 137 (CD137), anti OX 40, anti- clusters of differentiation 40 (CD40), or any other immune checkpoint inhibitor). 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. Participants 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.
研究组 & 干预措施
OPDIVO 10 mg/mL concentrate for solution for infusion., OPDIVO 10 mg/mL concentrate for solution for infusion., OPDIVO 10 mg/mL concentrate for solution for infusion., OPDIVO 10 mg/mL concentrate for solution for infusion.
Comparator
干预措施: OPDIVO 10 mg/mL concentrate for solution for infusion. (Drug)
GS-1811 150 mg/vial concentrate for solution for infusion, GS-1811
Test
干预措施: GS-1811 150 mg/vial concentrate for solution for infusion (Drug)
Avastin 25 mg/ml concentrate for solution for infusion., Avastin 25 mg/ml concentrate for solution for infusion.
Comparator
干预措施: Avastin 25 mg/ml concentrate for solution for infusion. (Drug)
Lonsurf 15 mg/6.14 mg film-coated tablets, Lonsurf 15 mg/6.14 mg film-coated tablets, Lonsurf 15 mg/6.14 mg film-coated tablets
Comparator
干预措施: Lonsurf 15 mg/6.14 mg film-coated tablets (Drug)
GS-1811 150 mg/vial concentrate for solution for infusion, GS-1811
Test
干预措施: GS-1811 (Drug)
结局指标
主要结局
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.
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
- DOR is measured from the time of first response (CR or PR) as assessed by investigator, per RECIST Version 1.1 until the date of first documented progressive disease (PD) or death, whichever comes first.
- PFS is the time from date of randomization until PD or death from any cause, whichever comes first as assessed by the investigator according to RECIST Version 1.1.
- OS is length of time from randomization until the date of death from any cause.
- The incidence, severity, seriousness, and relatedness of treatment-emergent adverse events (TEAEs) and incidence and severity of clinical laboratory abnormalities graded according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
- Serum concentration of DEN and estimated PK parameters (eg, Cmax and AUCall)
- Percentage of treatment-emergent DEN ADA positive and ADA negative participants
研究者
EU CT Support
Scientific
Gilead Sciences Inc.
研究点 (21)
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