A Phase 1/2, Open-Label, Multicenter Study of MDK-703 as a Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With Advanced or Metastatic Solid Tumors (ORCHID-1)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 6
- 主要终点
- Dose Limiting Toxicities (DLT)
研究概览
简要总结
This is an open-label, dose escalation and dose expansion study of MDK-703 as a monotherapy and in combination with other cancer therapies in adult study participants with advanced or metastatic solid tumors.
详细描述
This is a Phase 1/2, open-label, multicenter, dose escalation and dose expansion study evaluating MDK-703 in adult study participants with advanced or metastatic solid tumors. This study will initially commence with dose escalation to evaluate the safety/tolerability of MDK-703 as a monotherapy and in combination with other cancer therapies. Once the monotherapy and/or combination therapy maximum tolerated dose (MTD), optimal biological dose (OBD), and/or recommended dose (RD) has been determined, then dose expansion of MDK-703 may commence in select populations of interest. The study will also evaluate the anti-tumor activity and pharmacokinetic (PK) and pharmacodynamic (PD) profiles of MDK-703 as a monotherapy and in combination with other cancer therapies.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Measurable disease per RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate cardiovascular, hematological, liver, and renal function.
- •Prior anti-cancer therapy is allowed as long as any treatment related toxicity is resolved to an appropriate level.
- •Females of childbearing potential and men who are not surgically sterile must agree to use medically-accepted method of birth control during the study.
- •[Females] Negative serum pregnancy test within 14 days prior to initiating study treatment.
- •[Males] Agreement to refrain from donating or banking sperm during the treatment period.
排除标准
- •Treated with anti-cancer therapy or an investigational agent within 2 weeks or 5 half-lives prior to first dose, whichever is shorter; or within 4 weeks for immunotherapy.
- •Unresolved toxicities from prior systemic therapy greater than NCI CTCAE grade 1 at time of first dose, except alopecia, vitiligo, and grade 2 neuropathy due to prior chemotherapy.
- •Radiotherapy within 14 days prior to first dose of study drug.
- •Major surgery within 30 days prior to first dose of study drug, or anticipation of major surgery during study treatment.
- •Active autoimmune disease requiring systemic treatment within the past 3 months or have a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents.
- •Primary central nervous system (CNS) disease or leptomeningeal disease.
- •Impaired cardiovascular function or clinically significant cardiovascular disease.
- •Uncontrolled diabetes mellitus or other uncontrolled immune-related endocrinopathies.
- •Abnormal pulmonary function within the previous 6 months, including history of pneumonitis, active pneumonitis, interstitial lung disease requiring the use of steroids, idiopathic pulmonary fibrosis, active pleural effusion, severe dyspnea at rest or requiring supplementary oxygen therapy.
- •History of allogenic, bone marrow, or solid organ transplant.
- •History of cerebrovascular events within 6 months prior to first dose.
- •Human immunodeficiency virus (HIV) infection or active infection with hepatitis C; uncontrolled hepatitis B infection.
- •Clinically significant bleeding within 2 weeks prior to first dose (e.g., gastrointestinal bleeding, intracranial hemorrhage).
- •Prior diagnosis of pulmonary embolism within 3 months prior to first dose.
- •Known intolerance, hypersensitivity, or contraindication to any components of MDK-703 or checkpoint inhibitors for applicable cohorts.
- •History of other malignancy within 5 years prior to first dose, except for patients who are disease-free for >2 years after treatment with curative intent or who have carcinoma in situ which has been excised.
- •Any serious medical condition (including pre-existing autoimmune disease or inflammatory disorder), laboratory abnormality, psychiatric condition, or any other significant or unstable concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy or would make the subject inappropriate for the study.
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
研究组 & 干预措施
MDK-703 Monotherapy
MDK-703 will be administered in sequential ascending doses as a monotherapy until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: MDK-703 (Drug)
MDK-703 in combination with a checkpoint inhibitor
MDK-703 will be administered in sequential ascending doses in combination with a checkpoint inhibitor until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: MDK-703 (Drug)
MDK-703 in combination with a checkpoint inhibitor
MDK-703 will be administered in sequential ascending doses in combination with a checkpoint inhibitor until unacceptable toxicity, disease progression, or withdrawal of consent.
干预措施: Checkpoint Inhibitor, Immune (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLT)
时间窗: Assessed up to 24 months
Based on toxicities observed from time of first dose through first cycle of treatment
Optimal biological dose (OBD)
时间窗: Assessed up to 24 months
Based on toxicities observed
Recommended dose (RD)
时间窗: Assessed up to 24 months
Based on toxicities observed
Maximum tolerated dose (MTD)
时间窗: Assessed up to 24 months
Based on toxicities observed
Adverse events (AE)
时间窗: Assessed up to 24 months
Incidence and severity of treatment-emergent AEs and serious AEs as assessed by CTCAE v5.0
次要结局
- Duration of Response (DOR)(Assessed up to 24 months)
- Objective Response Rate (ORR)(Assessed up to 24 months)
- Time to achieve maximum blood concentration(Assessed up to 24 months)
- Overall Survival (OS)(Assessed up to 24 months)
- Blood concentration of MDK-703(Assessed up to 24 months)
- Time to Response (TTR)(Assessed up to 24 months)
- Disease Control Rate (DCR)(Assessed up to 24 months)
- Progression-Free Survival (PFS)(Assessed up to 24 months)