A Phase 1, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-901 as Monotherapy in Patients With Selected Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 13
- 主要终点
- Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs)
研究概览
简要总结
The primary objectives of this study are to identify the recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD), and to characterize the safety and the tolerability of ADCT-901.
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
- •Pathologic diagnosis of selected solid tumor malignancy that is locally advanced or metastatic at time of Screening: cholangiocarcinoma, ovarian/fallopian tube cancers, prostate cancer, renal cell carcinoma, and triple negative breast cancer (TNBC).
- •Note: Histologic variants of prostate cancer, including neuroendocrine features and small cell carcinoma of the prostate are permitted.
- •Participants who are refractory to or intolerant to existing therapy(ies) known to provide clinical benefit for their condition per Investigator judgment.
- •Participants with measurable disease as determined by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1:
- •Note 1: Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that can be evaluated by cross sectional imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) can be considered as measurable lesions only if the soft tissue component meets the definition of measurability per RECIST v1.
- •Note 2: Prostate cancer participants without measurable lesions will be accepted, with evidence of bone metastatic disease on radiographic examination, whether from bone scan or other imaging modality, and prostate specific antigen (PSA) ≥2.0 ng/mL.
排除标准
- •History of active infection (requiring intravenous [IV] antibiotics, IV antiviral or IV antifungal treatment within 4 weeks of cycle 1, day 1 [C1D1]).
- •Symptomatic central nervous system (CNS) metastases or evidence of leptomeningeal disease (brain MRI or previously documented cerebrospinal fluid cytology). Previously treated asymptomatic CNS metastases are permitted provided that the last treatment (systemic anticancer therapy and/or local radiotherapy) was completed ≥4 weeks prior to C1D1 except usage of low dose of steroids on a taper (i.e., up to 10 mg prednisone or equivalent on Day 1 and consecutive days is permissible if being tapered down). Participants with discrete dural metastases are eligible.
- •Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or any serosal effusion that is either requiring drainage or associated with shortness of breath).
- •Active diarrhea ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or a medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease).
- •Active or clinically significant ocular surface disease at baseline. An ocular evaluation is to be confirmed by an ophthalmologist at screening. Participants with any prior episode of cicatricial conjunctivitis (as evaluated by the investigator) are ineligible.
- •Note: Mild dry eye syndrome or blepharitis managed with artificial tear drops, without injection or epithelial changes, are not exclusionary.
- •Use of any other experimental medication within 14 days prior to start of study drug (C1D1).
研究组 & 干预措施
Part 1: Dose Escalation
In Part 1 (dose escalation) participants with selected advanced solid tumors will receive escalating doses of ADCT-901 as monotherapy. Participants can receive ADCT-901 until disease progression, adverse event (AE), or other discontinuation criteria, whichever occurs first.
干预措施: ADCT-901 (Drug)
Part 2: Dose Expansion
In Part 2 (dose expansion), participants will receive ADCT-901 monotherapy at the dose identified as the RP2D/MTD in Part 1 (dose escalation).
Participants will be split into two groups:
Group 1: An indication for which ADCT-901 showed in Part 1 to have preliminary activity.
Group 2: A group of participants with Part 1 indications, except for the one selected in Group 1 of Part 2. No more than 30% of participants with the same indication are allowed in this basket group.
Participants can receive ADCT-901 until disease progression, AE, or other discontinuation criteria, whichever occurs first.
干预措施: ADCT-901 (Drug)
结局指标
主要结局
Safety and Tolerability as Assessed by Number of Participants with Adverse Events (AEs)
时间窗: Up to approximately 2.5 years
Adverse events (AEs) and serious adverse events (SAEs) were defined as any untoward medical occurrence in participants whether or not considered related to the investigational medicinal product. Any clinically significant changes in vital signs, laboratory values, 12-lead electrocardiogram (ECG) and Eastern Cooperative Oncology Group (ECOG) performance status results will be recorded as AEs and SAEs.
Number of Participants Who Experience a Dose Reduction
时间窗: Up to approximately 2.5 years
Number of Participants Who Experience a Dose Limiting Toxicity (DLT) During the Dose-Escalation Phase
时间窗: Day 1 to Day 21
Number of Participants Who Experience a Dose Interruption
时间窗: Up to approximately 2.5 years
次要结局
- Overall Survival (OS)(Up to approximately 2.5 years)
- Maximum Concentration (Cmax) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Up to approximately 2.5 years)
- Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUClast) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Up to approximately 2.5 years)
- Apparent Terminal Elimination Half-Life (Thalf) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Up to approximately 2.5 years)
- Apparent Clearance (CL) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Up to approximately 2.5 years)
- Area Under the Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Up to approximately 2.5 years)
- Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Up to approximately 2.5 years)
- Number of Participants with an Anti-drug Antibody (ADA) Response to ADCT-901(Up to approximately 2.5 years)
- Overall Response Rate (ORR)(Up to approximately 2.5 years)
- Duration of Response (DOR)(Up to approximately 2.5 years)
- Progression-Free Survival (PFS)(Up to approximately 2.5 years)
- Time to Maximum Concentration (Tmax) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Up to approximately 2.5 years)
- Accumulation Index (AI) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Up to approximately 2.5 years)
- Apparent Volume of Distribution (Vss) of ADCT-901 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Up to approximately 2.5 years)