NCT05007782招募中1 期
A Phase 1 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of Denikitug (GS-1811), an Afucosylated Anti-CCR8 Monoclonal Antibody, as Monotherapy and in Combination With an Anti-PD-1 Monoclonal Antibody in Adults With Advanced Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 416
- 试验地点
- 25
- 主要终点
- Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0
研究概览
简要总结
This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of denikitug (also known as GS-1811) as monotherapy and in combination with zimberelimab in participants with advanced solid tumors.
This study will be conducted in 6 parts (Parts A, B, and E: monotherapy, Parts C and D: combination therapy, and Part F for both monotherapy and combination therapy) in participants with advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or in participants with select solid tumors.
详细描述
Part D allocation for 1 cohort will be randomized.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Part A: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
- •Part B: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
- •Part C: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or whose disease is indicated for anti- programmed cell death protein 1 or programmed cell death ligand 1 (PD-[L]1) monoclonal antibody monotherapy.
- •Part D: Individuals with pathologically confirmed select advanced solid tumors.
- •Part E: Individuals with pathologically confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatment known to confer clinical benefit.
- •Part F: Individuals with pathologically-confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatments known to confer clinical benefit; or, for participants who will undergo combination therapy, have disease which is indicated for anti-PD-(L)1 mAb monotherapy.
- •Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D, E, and F.
- •Adequate organ function.
- •Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception.
- •Tissue requirement:
- •Parts A, C, D, E and F: Must provide pre-treatment adequate tumor tissue sample prior to enrollment.
- •Part B and select participants in Parts C and F: Must have fresh pre-treatment and on-treatment biopsies for biomarker analysis.
排除标准
- •Concurrent anticancer treatment.
- •Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: immunotherapy or biologic therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14 days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21 days).
- •Any prior CCR8 directed therapy.
- •Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed.
- •Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected carcinoma in situ, localized prostate cancer, or superficial bladder cancer after undergoing potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease-free for > 2 years.
- •History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy.
- •History of autoimmune disease or active autoimmune disease requiring systemic treatment within 2 years.
- •History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
- •Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires IV antibiotics.
- •Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
- •Positive serum pregnancy test or breastfeeding female.
- •Live vaccines within 30 days prior to first dose.
- •Significant cardiovascular disease.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part D: Denikitug + Zimberelimab Dose Expansion
Experimental
干预措施: Zimberelimab (Drug)
Part E: Denikitug Monotherapy Dose Expansion
Experimental
干预措施: Denikitug (Drug)
Part A - Denikitug Dose Escalation
Experimental
干预措施: Denikitug (Drug)
Part B - Mandatory Paired Tumor Biopsy
Experimental
干预措施: Denikitug (Drug)
Part C: Denikitug + Zimberelimab Dose Escalation
Experimental
干预措施: Denikitug (Drug)
Part C: Denikitug + Zimberelimab Dose Escalation
Experimental
干预措施: Zimberelimab (Drug)
Part D: Denikitug + Zimberelimab Dose Expansion
Experimental
干预措施: Denikitug (Drug)
Part F: Denikitug Monotherapy and In Combination With Zimberelimab In Select Dose and Schedule
Experimental
干预措施: Denikitug (Drug)
Part F: Denikitug Monotherapy and In Combination With Zimberelimab In Select Dose and Schedule
Experimental
干预措施: Zimberelimab (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0
时间窗: First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
时间窗: First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Part A and C
时间窗: Day 1 Through Day 21
次要结局
- Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for Denikitug(Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days)
- PK Parameter: Minimum Observed Concentration (Cmin) for Denikitug(Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days)
- PK Parameter: Time of Maximum Observed Concentration (Tmax) for Denikitug(Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days)
- PK Parameter: Area Under the Concentration-time Curve (AUC) for Denikitug(Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days)
- Percentage of Participants who Developed Antidrug Antibody (ADA) Against Denikitug(Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days)
- Objective response rate (ORR) in Part D(Day 1 Up to End of Treatment (24 months))
- Disease control rate (DCR)(Day 1 Up to End of Treatment (24 months))
- Time to response (TTR)(Day 1 Up to End of Treatment (24 months))
- Duration of response (DOR)(Day 1 Up to End of Treatment (24 months))
- Progression-free survival (PFS)(Day 1 Up to End of Treatment (24 months))
研究者
研究点 (25)
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