A Phase 1/1b First-in-Human, Open Label, Dose Escalation and Cohort Expansion Study of MGC026 in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- MacroGenics
- 入组人数
- 250
- 试验地点
- 12
- 主要终点
- Number of participants with adverse events (AEs) and serious AEs (SAEs), AEs leading to dose delay, AEs leading to dose reduction, AEs leading to treatment discontinuations, AEs meeting criteria for dose limiting toxicity, and AEs of special interest.
研究概览
简要总结
The study is designed to understand the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of MGC026 in participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors The study has a dose escalation portion and a cohort expansion portion of the study.
Participants will receive MGC026 by intravenous (IV) infusion. The dose of MGC026 will be assigned at the time of enrollment. Participants may receive up to 35 treatments if there are no severe side effects and as long as the cancer does not get worse. Participants will be monitored for side effects, and progression of cancer, have blood samples collected for routing laboratory work, and blood samples collected for research purposes.
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
- •Adults ≥ 18 years old, able to provide informed consent
- •Adequate performance and laboratory parameters
- •Availability of archival or formalin-fixed paraffin-embedded tumor tissue sample. Participants may undergo a fresh tumor biopsy to obtain a specimen for testing if an archival tumor sample is not available. Participants with no available archival tissue sample who cannot safely undergo a fresh biopsy as determined by consultation between the sponsor and investigator are eligible
- •Unresectable, locally advanced or metastatic solid tumors including: squamous cell cancer (SCC) of the head and neck, esophageal SCC, squamous and non-squamous non-small cell lung cancer, small cell lung cancer, bladder cancer, sarcoma, endometrial cancer, melanoma, castration resistant prostate cancer, breast cancer, ovarian cancer, cervical cancer, colorectal cancer gastric or gastroesophageal cancer, pancreatic carcinoma, clear cell renal cell cancer or hepatocellular cancer.
- •Measurable disease per RECIST v1.
- •Participants with metastatic CRPC without measurable disease are eligible.
- •Must be willing to use highly effective methods of birth control from the time of consent through 7 months after discontinuation of MGC
- •Not pregnant or breastfeeding.
排除标准
- •Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures.
- •Another cancer that required treatment within the past 2 years, with the exception of those with low risk of cancer spreading or death such as adequately treated non melanomatous skin cancer, localized prostate cancer (Gleason Score < 6), or carcinoma in situ.
- •Patients with history of prior central nervous system (CNS) metastasis must have been treated, be asymptomatic, and not have concurrent treatment for CNS disease, progression of CNS metastases on magnetic resonance imaging, computed tomography or positron emission tomography, or history of leptomeningeal disease or cord compression at the time of enrollment.
- •Treatment with surgery, systemic cancer therapy, immunotherapy, chimeric antigen receptor-T therapy, or anti-hormonal within protocol specified intervals.
- •Prior treatment with any B7-H3 targeted agent for cancer or any ADC with a topoisomerase payload.
- •Prior autologous or allogeneic stem cell or solid organ transplant.
- •Clinically significant cardiovascular, pulmonary, or gastrointestinal disorders.
- •Active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 1 week of first study drug administration.
- •Known history of hepatitis B or C infection or known positive test for hepatitis B surface antigen or core antigen, or hepatitis C polymerase chain reaction.
- •Known positive testing for human immunodeficiency virus or history of acquired immune deficiency syndrome.
- •History of primary immunodeficiency.
- •Major trauma or major surgery within 4 weeks of first study drug administration.
- •Known hypersensitivity to recombinant proteins.
研究组 & 干预措施
Cohort 5
干预措施: MGC026 Dose Escalation (Biological)
Expansion Cohort 6
干预措施: MGC026 Dose for Expansion (Biological)
Cohort 1
MGC026 is a topoisomerase 1 inhibitor (TOP1i)-based ADC that targets B7-H3 administered IV every 3 weeks.
干预措施: MGC026 Dose Escalation (Biological)
Cohort 2
干预措施: MGC026 Dose Escalation (Biological)
Cohort 3
干预措施: MGC026 Dose Escalation (Biological)
Cohort 4
干预措施: MGC026 Dose Escalation (Biological)
Cohort 6
干预措施: MGC026 Dose Escalation (Biological)
Expansion cohort 1
干预措施: MGC026 Dose for Expansion (Biological)
Expansion cohort 2
干预措施: MGC026 Dose for Expansion (Biological)
Expansion cohort 3
干预措施: MGC026 Dose for Expansion (Biological)
Expansion cohort 4
干预措施: MGC026 Dose for Expansion (Biological)
Expansion Cohort 5
干预措施: MGC026 Dose for Expansion (Biological)
结局指标
主要结局
Number of participants with adverse events (AEs) and serious AEs (SAEs), AEs leading to dose delay, AEs leading to dose reduction, AEs leading to treatment discontinuations, AEs meeting criteria for dose limiting toxicity, and AEs of special interest.
时间窗: Throughout the study, up to 135 weeks
次要结局
- Overall response rate in advanced solid tumors(Throughout the study, up to 135 weeks)
- Duration of response (DoR) in advanced solid tumors(Throughout the study, up to 135 weeks)
- ORR rate in metastatic castration resistant prostate cancer (mCRPC)(Throughout the study, up to 135 weeks)
- DoR in mCRPC(Throughout the study, up to 135 weeks)
- Mean (standard deviation [SD]) of MGC026 total and conjugated antibody maximum serum concentration (Cmax)(Cycle 1 Day 1: at baseline, end of infusion (EOI) approximately 1 hr, 4hrs after EOI, Day 2 and Day 4.)
- Mean (standard deviation [SD]) of MGC026 unconjugated payload Cmax(Cycle 1 Day 1: at baseline, end of infusion (EOI) approximately 1 hr, 4hrs after EOI, Day 2 and Day 4.)
- Mean (SD) of MGC026 total and conjugated antibody area under the time concentration curve (AUC)(Cycle 1 Day 1: at baseline, EOI approximately 1 hr, 4hrs after EOI, Day 2, Day 4, Day 8, Day 15, and predose Cycle 2 Day 1)
- Mean (SD) of MGC026 unconjugated payload AUC(Cycle 1 Day 1: at baseline, EOI approximately 1 hr, 4hrs after EOI, Day 2, Day 4, Day 8, Day 15, and predose Cycle 2 Day 1)
- Number of participants who develop anti-MGC026 antibodies (immunogenicity)(Day 1, Day 15, and Day 1 of every 21-day cycle, throughout the study, average of 1 year.)