A Phase 1b, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Mipasetamab Uzoptirine (ADCT-601) Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With Selected Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 128
- 试验地点
- 14
- 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 objective of this study is to identify the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD), and characterize the safety and tolerability of ADCT-601 monotherapy and in combination with gemcitabine.
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
- •Male or female participant aged 18 years or older.
- •Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of screening:
- •Combination therapy arms: Selected sarcoma indications from the following 2 separate categories.
- •Soft tissue sarcoma: leiomyosarcoma, liposarcoma, undifferentiated pleomorphic sarcoma (UPS; covering malignant fibrous histiocytoma) and synovial sarcoma.
- •Bone sarcoma: Ewing's sarcoma (including extraskeletal), osteosarcoma, and chondrosarcoma.
- •Monotherapy arms:
- •Sarcoma indications (including those listed for combination therapy arms) regardless of AXL gene amplification status.
- •NSCLC regardless of AXL gene amplification status.
- •Solid tumors (lymphomas participants are excluded) with known AXL gene amplification.
- •Combination therapy arms: Sarcoma indications and PAAD.
- •Monotherapy arms: PAAD, NSCLC and solid tumors with AXL expression.
- •Participants who are refractory to or intolerant to available standard 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.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 -
- •PAAD only: Royal Marsden Hospital Prognostic Score 0 - 1.
排除标准
- •History of recent 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 magnetic resonance imaging [MRI] or previously documented cerebrospinal fluid [CSF] 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 Day 1 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).
- •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, ADCT-601 Combination Therapy
In Part 1 (dose escalation), participants with selected sarcoma indications will receive escalating doses of ADCT-601 in combination with gemcitabine.
干预措施: ADCT-601 (Drug)
Part 1: Dose Escalation, ADCT-601 Combination Therapy
In Part 1 (dose escalation), participants with selected sarcoma indications will receive escalating doses of ADCT-601 in combination with gemcitabine.
干预措施: Gemcitabine (Drug)
Part 1: Dose Escalation, ADCT-601 Monotherapy
In Part 1 (dose escalation), participants with sarcoma indications (regardless of AXL gene amplification status), non-small-cell lung cancer (NSCLC) (regardless of AXL gene amplification status), and solid tumors with AXL gene amplification, will receive ADCT-601 monotherapy.
干预措施: ADCT-601 (Drug)
Part 2: Dose Expansion, ADCT-601 Combination Therapy
In Part 2 (dose expansion), participants with selected sarcoma indications will receive ADCT-601 in combination with gemcitabine.
Participants will be split into 3 cohorts:
Cohorts 5 and 6: Sarcoma indications.
Cohort 7: Pancreatic cancer.
干预措施: ADCT-601 (Drug)
Part 2: Dose Expansion, ADCT-601 Combination Therapy
In Part 2 (dose expansion), participants with selected sarcoma indications will receive ADCT-601 in combination with gemcitabine.
Participants will be split into 3 cohorts:
Cohorts 5 and 6: Sarcoma indications.
Cohort 7: Pancreatic cancer.
干预措施: Gemcitabine (Drug)
Part 2: Dose Expansion, ADCT-601 Monotherapy
In Part 2 (dose expansion), participants with a selected indication will receive ADCT-601 monotherapy.
Participants will be split into cohorts:
Cohort 1: Soft tissue sarcoma (STS).
Cohort 2: Pancreatic adenocarcinoma (PAAD).
Cohort 3: NSCLC.
Cohort 4: Solid tumors with known AXL expression.
干预措施: ADCT-601 (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 years
Adverse events (AEs) and serious adverse events (SAEs) are 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 Limiting Toxicity (DLT)
时间窗: Day 1 to Day 21
Number of Participants who Experience a Dose Interruption
时间窗: Up to approximately 2 years
Number of Participants who Experience a Dose Reduction
时间窗: Up to approximately 2 years
次要结局
- Apparent Terminal Elimination Half-life (T1/2) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Day 1 up to approximately 2 years)
- Time to Maximum Concentration (Tmax) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Day 1 up to approximately 2 years)
- Number of Participants With an Anti-drug Antibody (ADA) Response to ADCT-601(Day 1 up to approximately 2 years)
- Duration of Response (DOR)(Up to approximately 2 years)
- Overall Survival (OS)(Up to approximately 2 years)
- Overall Response Rate (ORR)(Up to approximately 2 years)
- Progression-Free Survival (PFS)(Up to approximately 2 years)
- Serum Concentration of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199(Day 1 up to approximately 2 years)
- Maximum Concentration (Cmax) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Day 1 up to approximately 2 years)
- Apparent Clearance (CL) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Day 1 up to approximately 2 years)
- Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Day 1 up to approximately 2 years)
- Area Under the Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Day 1 up to approximately 2 years)
- Area Under the Concentration-time Curve from Time Zero to Infinity (AUCinf) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Day 1 up to approximately 2 years)
- Number of Participants With Anti-drug Antibody (ADA) Titers to ADCT-601(Day 1 up to approximately 2 years)
- Apparent Steady-state Volume of Distribution (Vss) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Day 1 up to approximately 2 years)
- Accumulation Index (AI) of ADCT-601 Total Antibody, Pyrrolobenzodiazepine (PBD)-Conjugated Antibody, and Unconjugated Warhead SG3199 in Serum(Day 1 up to approximately 2 years)